2,093 results on '"SOMATOMEDIN"'
Search Results
2. Insulin-Like Growth Factor-1: A Promising Therapeutic Target for Peripheral Nerve Injury
- Author
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Benjamin R. Slavin, Karim A. Sarhane, Nicholas von Guionneau, Phillip J. Hanwright, Chenhu Qiu, Hai-Quan Mao, Ahmet Höke, and Sami H. Tuffaha
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0301 basic medicine ,Histology ,medicine.medical_treatment ,PNI ,Biomedical Engineering ,nanoparticle carrier ,Sensory system ,Bioengineering ,Review ,Bioinformatics ,03 medical and health sciences ,Insulin-like growth factor ,0302 clinical medicine ,Peripheral nerve ,Myocyte ,Medicine ,peripheral nerve injury ,nerve regeneration ,Surgical repair ,business.industry ,Bioengineering and Biotechnology ,Regenerative process ,Somatomedin ,somatomedin C ,030104 developmental biology ,Peripheral nerve injury ,IGF-1 ,business ,TP248.13-248.65 ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.
- Published
- 2021
3. Auto-regulatory J-domain interactions control Hsp70 recruitment to the DnaJB8 chaperone
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Irina Matlahov, Sofia Bali, Bryan D. Ryder, Lukasz A. Joachimiak, Patrick C.A. van der Wel, and Jaime Vaquer-Alicea
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animal structures ,biology ,DNA synthesis ,Chemistry ,Insulin ,medicine.medical_treatment ,Glucose transporter ,Biological activity ,Stimulation ,Somatomedin ,nervous system diseases ,Cell biology ,Hsp70 ,stomatognathic system ,Chaperone (protein) ,mental disorders ,parasitic diseases ,biology.protein ,medicine - Abstract
Multiplication-stimulating activity (MSA) produced by Buffalo rat liver cells (BRL-3A) in culture is related to the somatomedin family of growth regulatory polypeptides. MSA will stimulate glucose transport and DNA synthesis in normal chicken embryo fibroblasts (CEF) at concentrations of 10-200 ng/ml. MSA found in BRL-3A-conditioned medium, like the somatomedins in serum, does not exist as the free hormone but is bound to a specific high molecular weight carrier protein. In this report we demonstrate that purified MSA carrier protein (MCP) inhibits the biological activity of MSA on CEF as measured by the stimulation of glucose transport and DNA synthesis. In addition, purified MCP competitively inhibits the binding of 125I-labeled MSA to these cells. In control experiments in which insulin was used as the mitogenic agent, MCP had no effect on these biological responses. These results indicate that the inhibitory effect of MCP is the result of specific interaction with MSA and support the hypothesis that cells may be unresponsive to somatomedins bound to their serum carrier proteins.
- Published
- 2020
4. The Insulin-Like Growth Factor-1 (IGF1) System as a Potential Biomarker for Nutritional Status and Growth Rate in Pacific Rockfish (SEBASTES SPP.)
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Nicole L Hack
- Subjects
medicine.medical_specialty ,biology ,medicine.medical_treatment ,Nutritional status ,Growth hormone ,biology.organism_classification ,Somatomedin ,Insulin-like growth factor ,Rockfish ,Endocrinology ,Internal medicine ,medicine ,Biomarker (medicine) ,Sebastes ,Growth rate - Published
- 2019
5. 40 YEARS OF IGF1: Insulin-like growth factors: actions on the skeleton
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Clifford J. Rosen, Shoshana Yakar, and Haim Werner
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0301 basic medicine ,Bone growth ,medicine.medical_specialty ,Growth factor ,medicine.medical_treatment ,Osteoblast ,Biology ,Somatomedin ,03 medical and health sciences ,Paracrine signalling ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Osteoclast ,Internal medicine ,Osteocyte ,medicine ,Autocrine signalling ,Molecular Biology - Abstract
The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of theIgf1andIgf2genes in temporal and spatial manners. The GH/IGF axis, acting in an endocrine and autocrine/paracrine fashion, is the major axis controlling skeletal growth. Studies in rodents have clearly shown that IGFs regulate bone length of the appendicular skeleton evidenced by changes in chondrocytes of the proliferative and hypertrophic zones of the growth plate. IGFs affect radial bone growth and regulate cortical and trabecular bone properties via their effects on osteoblast, osteocyte and osteoclast function. Interactions of the IGFs with sex steroid hormones and the parathyroid hormone demonstrate the significance and complexity of the IGF axis in the skeleton. Finally, IGFs have been implicated in skeletal aging. Decreases in serum IGFs during aging have been correlated with reductions in bone mineral density and increased fracture risk. This review highlights many of the most relevant studies in the IGF research landscape, focusing in particular on IGFs effects on the skeleton.
- Published
- 2018
6. Effect of growth hormone and somatomedin-C axis on fracture healing
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Hakan Kocaoğlu, Özgür Doğan, Özgür Kaya, Batuhan Gencer, Emrah Caliskan, and Ali Biçimoğlu
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Medicine (General) ,medicine.medical_specialty ,iatrogenic fracture ,RD1-811 ,medicine.medical_treatment ,Urology ,Bone healing ,Osteotomy ,somatomedin c ,i̇atrojenik kırık ,R5-920 ,büyüme hormonu ,medicine ,Pathological ,kırık iyileşmesi ,business.industry ,Acute-phase protein ,Soft tissue ,fracture healing ,Somatomedin ,growth hormone ,Medicine ,Surgery ,business ,Cohort study ,Hormone - Abstract
Aim: Many studies have examined the effects of different calciotropic hormones on fracture healing, whereas few studies focus on growth factors. Local detection of somatomedin C (IGF-1) in fracture callus, application of growth hormone (GH) and IGF-1 as non-union treatment, and low GH and IGF-1 levels in osteoporotic fractures indicate that these hormones are effective in fracture healing. However, most of these studies are based on post fracture GH and IGF-1 levels. GH and IGF-1 are also involved in acute phase response and can change due to trauma. The aim of this study is to investigate the change in GH and IGF-1 levels in patients treated with osteotomy, in which an iatrogenic fracture is created, and to evaluate the effect of these hormones on fracture healing by comparing the results before and after the fractures. Methods: Patients who were diagnosed with developmental dysplasia of the hip and underwent surgery between 2014-2015 were prospectively followed for this cohort study. Forty-one patients were included, and two groups were formed. Patients who underwent open reduction and soft tissue release without osteotomy (n=20) were included in the first group. Patients who underwent pelvic osteotomy (n=21), in which iatrogenic fractures were created, were included in the second group. Blood samples were obtained from all patients pre-operatively and on the 1st and 28th postoperative days. Friedman and Mann-Whitney U tests were used for statistical analysis. Results: Mean age of the first group, comprising 19 females (95%) and 1 male (5%), was 11.25 months (Range: 6-25 months). Mean age of the second group, including 17 females (85.7%) and 4 males (14.3%), was 74.4 months (Range: 24-120 months). While there was no significant difference between pre- and postoperative GH values in the first group (P=0.05), postoperative GH levels were significantly higher than preoperative GH levels in the second group (P
- Published
- 2019
7. Leucine Supplementation Does Not Restore Diminished Skeletal Muscle Satellite Cell Abundance and Myonuclear Accretion When Protein Intake Is Limiting in Neonatal Pigs
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Daniel A Columbus, Ryan Fleischmann, Hanh V. Nguyen, Marko Rudar, Julia Steinhoff-Wagner, Teresa A. Davis, Agus Suryawan, and Marta L. Fiorotto
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0301 basic medicine ,medicine.medical_specialty ,Satellite Cells, Skeletal Muscle ,Swine ,medicine.medical_treatment ,Medicine (miscellaneous) ,03 medical and health sciences ,0302 clinical medicine ,Suidae ,Leucine ,Internal medicine ,medicine ,Myocyte ,Animals ,Muscle, Skeletal ,Insulin-like growth factor 1 receptor ,Nutrition and Dietetics ,biology ,Chemistry ,Growth factor ,Skeletal muscle ,Biochemical, Molecular, and Genetic Mechanisms ,biology.organism_classification ,Somatomedin ,Animal Feed ,Diet ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Postprandial ,Animals, Newborn ,Dietary Supplements ,Animal Nutritional Physiological Phenomena ,Dietary Proteins ,030217 neurology & neurosurgery - Abstract
BACKGROUND: Rapid growth of skeletal muscle in the neonate requires the coordination of protein deposition and myonuclear accretion. During this developmental stage, muscle protein synthesis is highly sensitive to amino acid supply, especially Leu, but we do not know if this is true for satellite cells, the source of muscle fiber myonuclei. OBJECTIVE: We examined whether dietary protein restriction reduces myonuclear accretion in the neonatal pig, and if any reduction in myonuclear accretion is mitigated by restoring Leu intake. METHODS: Neonatal pigs (1.53 ± 0.2 kg) were fitted with jugular vein and gastric catheters and fed 1 of 3 isoenergetic milk replacers every 4 h for 21 d: high protein [HP; 22.5 g protein/(kg/d); n= 8]; restricted protein [RP; 11.2 g protein/(kg/d); n= 10]; or restricted protein with Leu [RPL; 12.0 g protein/(kg/d); n= 10]. Pigs were administered 5-bromo-2’-deoxyuridine (BrdU; 15 mg/kg) intravenously every 12 h from days 6 to 8. Blood was sampled on days 6 and 21 to measure plasma Leu concentrations. On day 21, pigs were killed and the longissimus dorsi (LD) muscle was collected to measure cell morphometry, satellite cell abundance, myonuclear accretion, and insulin-like growth factor (IGF) system expression. RESULTS: Compared with HP pigs, postprandial plasma Leu concentration in RP pigs was 37% and 47% lower on days 6 and 21, respectively (P
- Published
- 2019
8. Intra-organ growth coordination in Drosophila is mediated by systemic ecdysone signaling
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Alexander W. Shingleton, Christopher D. Mirque, Rewatee H. Gokhale, and Takashi Hayashi
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0301 basic medicine ,Ecdysone ,medicine.medical_specialty ,medicine.medical_treatment ,Ecdysterone ,Biology ,Animals, Genetically Modified ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Somatomedins ,Internal medicine ,medicine ,Animals ,Wings, Animal ,Compartment (development) ,Molecular Biology ,Growth factor ,Organ Size ,Cell Biology ,Somatomedin ,Cell biology ,Imaginal disc ,030104 developmental biology ,Endocrinology ,Imaginal Discs ,chemistry ,Larva ,Drosophila ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Regulation of final organ size is a complex developmental process that involves the integration of systemic and organ-specific processes. Previously, we have shown that in developing Drosophila, perturbing the growth of one imaginal disc - the parts of a holometabolous larva that become the external adult organs - retards growth of other discs and delays development, resulting in tight inter-organ growth coordination and the generation of a correctly proportioned adult. Whether different parts of the same imaginal disc similarly coordinate their growth to generate a functioning adult organ is, however, unclear. In this study, we use the wing imaginal disc in Drosophila to study and identify mechanisms of intra-organ growth coordination. We generate larvae in which the two compartments of the wing imaginal disc have ostensibly different growth rates (wild-type or growth-perturbed). We find that there is tightly coordinated growth between the wild-type and growth-perturbed compartments, where growth of the wild-type compartment is retarded to match that of the growth-perturbed compartment. Crucially, this coordination is disrupted by application of exogenous 20-hydroxyecdysone (20E), which accelerates growth of the wild-type compartment. We further elucidate the role of 20E signaling in growth coordination by showing that in wild-type discs, compartment-autonomous up-regulation of 20E signaling accelerates compartment growth and disrupts coordination. Interestingly, growth acceleration through exogenous application of 20E is inhibited with suppression of the Insulin/Insulin-like Growth Factor Signaling (IIS) pathway. This suggests that an active IIS pathway is necessary for ecdysone to accelerate compartment growth. Collectively, our data indicate that discs utilize systemic mechanisms, specifically ecdysone signaling, to coordinate intra-organ growth.
- Published
- 2016
9. Leptin stimulates hepatic growth hormone receptor and insulin-like growth factor gene expression in a teleost fish, the hybrid striped bass
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Russell J. Borski, David A. Hurt, Jonathan D. Douros, and Eugene T. Won
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Leptin ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Growth hormone receptor ,Biology ,Energy homeostasis ,03 medical and health sciences ,Insulin-like growth factor ,Endocrinology ,Somatomedins ,Internal medicine ,medicine ,Animals ,Autocrine signalling ,Regulation of gene expression ,Leptin receptor ,Receptors, Somatotropin ,Somatomedin ,030104 developmental biology ,Gene Expression Regulation ,Liver ,Growth Hormone ,Bass ,Animal Science and Zoology ,hormones, hormone substitutes, and hormone antagonists - Abstract
Leptin is an anorexigenic peptide hormone that circulates as an indicator of adiposity in mammals, and functions to maintain energy homeostasis by balancing feeding and energy expenditure. In fish, leptin tends to be predominantly expressed in the liver, another important energy storing tissue, rather than in fat depots as it is in mammals. The liver also produces the majority of circulating insulin-like growth factors (IGFs), which comprise the mitogenic component of the growth hormone (GH)-IGF endocrine growth axis. Based on similar regulatory patterns of leptin and IGFs that we have documented in previous studies on hybrid striped bass (HSB: Morone saxatilis×Morone chrysops), and considering the co-localization of these peptides in the liver, we hypothesized that leptin might regulate the endocrine growth axis in a manner that helps coordinate somatic growth with energy availability. Using a HSB hepatocyte culture system to simulate autocrine or paracrine exposure that might occur within the liver, this study examines the potential for leptin to modulate metabolism and growth through regulation of IGF gene expression directly, or indirectly through the regulation of GH receptors (GHR), which mediate GH-induced IGF expression. First, we verified that GH (50nM) has a classical stimulatory effect on IGF-1 and additionally show it stimulates IGF-2 transcription in hepatocytes. Leptin (5 and/or 50nM) directly stimulated in vitro GHR2 gene expression within 8h of exposure, and both GHR1 and GHR2 as well as IGF-1 and IGF-2 gene expression after 24h. Cells were then co-incubated with submaximal concentrations of leptin and GH (25nM each) to test if they had a synergistic effect on IGF gene expression, possibly through increased GH sensitivity following GHR upregulation by leptin. In combination, however, the treatments only had an additive effect on stimulating IGF-1 mRNA despite their capacity to increase GHR mRNA abundance. This suggests that leptin's stimulatory effect on GHRs may be limited to enhancing transcription or mRNA stability rather than inducing full translation of functional receptors, at least within a 24-h time frame. Finally, leptin was injected IP (100ng/g and 1μg/gBW) to test the in vivo regulation of hepatic IGF-1 and GHR1 gene expression. The 100ng/g BW leptin dose significantly upregulated in vivo IGF-1 mRNA levels relative to controls after 24h of fasting, but neither dosage was effective at regulating GHR1 gene expression. These studies suggest that stimulation of growth axis component transcripts by leptin may be an important mechanism for coordinating somatic growth with nutritional state in these and perhaps other fish or vertebrates, and represent the first evidence of leptin regulating GHRs in vertebrates.
- Published
- 2016
10. The emerging role of insulin receptor isoforms in thyroid cancer: Clinical implications and new perspectives
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Veronica Vella and Roberta Malaguarnera
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0301 basic medicine ,medicine.medical_treatment ,Somatomedin ,Review ,medicine.disease_cause ,lcsh:Chemistry ,0302 clinical medicine ,Receptors ,Insulin ,Insulin-Like Growth Factor I ,Receptor ,Thyroid cancer ,lcsh:QH301-705.5 ,Spectroscopy ,Hepatocyte Growth Factor ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,Computer Science Applications ,IR-A/IGF2 autocrine loop ,030220 oncology & carcinogenesis ,Insulin/IGF system ,Neoplastic Stem Cells ,Hepatocyte growth factor ,Signal transduction ,medicine.drug ,Biology ,Hybrids receptors ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Discoidin Domain Receptor 1 ,medicine ,Animals ,Humans ,Thyroid Neoplasms ,Physical and Theoretical Chemistry ,Molecular Biology ,DDR1 ,Insulin receptor isoforms ,Thyroid cancer stem cells ,Receptor, Insulin ,Receptors, Somatomedin ,Organic Chemistry ,medicine.disease ,Insulin receptor ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer research ,biology.protein ,Carcinogenesis - Abstract
Thyroid cancer (TC) is the most common endocrine tumor. Although the majority of TCs show good prognoses, a minor proportion are aggressive and refractory to conventional therapies. So far, the molecular mechanisms underlying TC pathogenesis are incompletely understood. Evidence suggests that TC cells and their precursors are responsive to insulin and insulin-like growth factors (IGFs), and often overexpress receptors for insulin (IR) and IGF-1 (IGF-1R). IR exists in two isoforms, namely IR-A and IR-B. The first binds insulin and IGF-2, unlike IR-B, which only binds insulin. IR-A is preferentially expressed in prenatal life and contributes to development through IGF-2 action. Aggressive TC overexpresses IR-A, IGF-2, and IGF-1R. The over-activation of IR-A/IGF-2 loop in TC is associated with stem-like features and refractoriness to some targeted therapies. Importantly, both IR isoforms crosstalk with IGF-1R, giving rise to the formation of hybrids receptors (HR-A or HR-B). Other interactions have been demonstrated with other molecules such as the non-integrin collagen receptor, discoidin domain receptor 1 (DDR1), and the receptor for the hepatocyte growth factor (HGF), Met. These functional networks provide mechanisms for IR signaling diversification, which may also exert a role in TC stem cell biology, thereby contributing to TC initiation and progression. This review focuses on the molecular mechanisms by which deregulated IR isoforms and their crosstalk with other molecules and signaling pathways in TC cells and their precursors may contribute to thyroid carcinogenesis, progression, and resistance to conventional treatments. We also highlight how targeting these alterations starting from TC progenitors cells may represent new therapeutic strategies to improve the clinical management of advanced TCs.
- Published
- 2018
11. Insulin-like Growth Factors in a clinical setting: Review of IGF-I
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David Karasek, Jan Schovanek, Zdenek Frysak, and Maurizio Iacobone
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growth hormone deficiency ,somatomedins ,medicine.medical_treatment ,lcsh:Medicine ,insulin-like growth factor i ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Growth hormone deficiency ,igf binding proteins ,Acromegaly ,medicine ,Humans ,Clinical significance ,Adverse effect ,recombinant human growth hormone ,Mecasermin ,mecasermin ,business.industry ,Growth factor ,Insulin ,lcsh:R ,medicine.disease ,ii ,Somatomedin ,Recombinant Proteins ,acid labile subunit ,igf-i receptor ,human growth hormone ,acromegaly ,business ,insulin receptor isoform a ,medicine.drug - Abstract
Background and Aims: Interest in growth hormone (GH) is inextricably linked to the need for in depth understanding of the somatomedins (insulin-like growth factors) which are polypeptides structurally similar to insulin and with broad physiological activity. To date, the most commonly known is Insulin-Like Growth Factor I (IGF-I). Despite considerable current knowledge of IGF-I, however, its bioactivity is incompletely understood. Measurement of IGF-I is of the utmost importance in the diagnosis and treatment of, for example acromegaly and growth hormone deficiency. The development of recombinant IGF-I, has allowed its use in such cases. Clinical practice, however, shows that few young/adult patients will benefit from treatment with the rIGF-I, mecasermin, given the number of adverse effects found. This review focuses on current knowledge mainly related to IGF-I and the use of its recombinant form (rIGF-I) in clinical practice. Several functions of IGI-II have been elucidated but their clinical significance is unclear.
- Published
- 2015
12. The Relation between Concentric and Eccentric EXERCISE and the Carbohydrate Metabolism in Healthy Individuals
- Author
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Aleksandra Zebrowska
- Subjects
medicine.medical_specialty ,genetic structures ,business.industry ,Insulin ,medicine.medical_treatment ,General Medicine ,Venous blood ,Carbohydrate metabolism ,Concentric ,Somatomedin ,Endocrinology ,Eccentric exercise ,Internal medicine ,medicine ,Eccentric ,General Materials Science ,business ,Hormone - Abstract
The purpose of the present study was to determine the response of glucose (G), insulin (In) and insulin-like growth factor (IGF)-I to eccentric (ECC) vs. concentric (CON) resistance exercise in healthy trained and untrained subjects. Venous blood samples were drawn before and immediately after the test, and during 1-hour recovery for the determinations of hormonal and somatomedin concentrations. As compared to resting values, the maximal eccentric (ECC) resistance exercise test caused a significant decrease in G level (p
- Published
- 2015
13. Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia
- Author
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Sachiko Minamiguchi, Taro Funakoshi, Takahiro Horimatsu, Shin'ichi Miyamoto, Tomoko Yamabata, Manabu Muto, Yuzo Kodama, Tsutomu Chiba, Takashi Setoyama, and Miutsuhiro Nikaido
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Hypoglycemia ,Paraneoplastic Endocrine Syndromes ,Paracrine signalling ,Somatomedins ,Internal medicine ,medicine ,Humans ,Carcinoma, Small Cell ,Neoplasm Metastasis ,Autocrine signalling ,Neoplasm Staging ,Pharmacology ,geography ,Bedside to Bench Report ,geography.geographical_feature_category ,biology ,business.industry ,Insulin ,Growth factor ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,Islet ,medicine.disease ,Somatomedin ,Insulin receptor ,Treatment Outcome ,Endocrinology ,Oncology ,Colonic Neoplasms ,Molecular targets ,biology.protein ,Molecular Medicine ,Cell tumor ,Tomography, X-Ray Computed ,business - Abstract
Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia with a wide variety of solid tumors. It is considered to cause hypoglycemia by increasing the insulin-like bioactivity of the circulating insulin-like growth factor (IGF) system, however, the precise mechanism of hypoglycemia remains unclear. In this manuscript, we report on a patient suffering from NICTH caused by a small cell carcinoma of the colon. This is the first report focusing on the role of bioactive IGFs for this pathological condition. First, we demonstrated that the IGF signal pathway has been activated in this tumor in an autocrine and/or paracrine manner using immunohistochemical analysis. Second, we confirmed that bioactive IGFs in the patient's serum were increased using a modified kinase receptor activation assay, thus bioactive IGFs (mainly IGF-2) could be considered to play a major pathogenic role in enhanced hypoglycemic insulin-like activity. Third, increased IGF bioactivity in the patient's serum was completely inhibited by an anti-IGF neutralizing antibody in vitro. These results suggest that neutralization of bioactive IGFs might become a novel therapeutic strategy for NICTH to relieve the hypoglycemic symptoms together with the tumor suppressive effect.
- Published
- 2014
14. Viral Insulin/IGF-1–Like Peptides: Novel Regulators of Physiology and Pathophysiology?
- Author
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David M. Irwin
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Insulin ,medicine.medical_treatment ,Biology ,Somatomedin ,Pathophysiology ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Internal medicine ,medicine ,Signal transduction ,Receptor - Published
- 2018
15. Sleep and Insulin-Like Growth Factors in the Cardiovascular Health Study
- Author
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Petra Bůžková, Robert C. Kaplan, Neomi Shah, Anne B. Newman, Thomas E. Rohan, Daniel Tracy, and Thomas B. Rice
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Cohort Studies ,Somatomedins ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Sex Distribution ,Geriatric Assessment ,Aged ,Slow-wave sleep ,Sleep Apnea, Obstructive ,business.industry ,Insulin ,Growth factor ,Sleep apnea ,New Research ,medicine.disease ,Health Surveys ,Somatomedin ,Sleep in non-human animals ,United States ,respiratory tract diseases ,Insulin-Like Growth Factor Binding Protein 1 ,Obstructive sleep apnea ,Cross-Sectional Studies ,Insulin-Like Growth Factor Binding Protein 3 ,Endocrinology ,Neurology ,Cardiovascular Diseases ,Female ,Neurology (clinical) ,Sleep ,business ,Cohort study - Abstract
Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population.Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS).1,233 elderly participants from the CHS and SHHS.The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p0.01). As expected, slow wave sleep was better preserved in females compared to males (22% total sleep time vs. 9% total sleep time, p0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] ≥ 5/h) was more prevalent in males compared to females (60% vs. 46%, p0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI ≥ 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI ≥ 5 and15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts.
- Published
- 2013
16. Detection and identification of oxidized insulin-like growth factor-binding proteins and receptors in patients with colorectal carcinoma
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Olgica Nedić, Dragana Robajac, Goran Miljuš, Miloš Šunderić, Vesna Malenković, and Blagoje Đukanović
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medicine.medical_specialty ,Proteolysis ,medicine.medical_treatment ,Oxidative phosphorylation ,Plasma protein binding ,Biochemistry ,Receptor, IGF Type 2 ,Insulin-like growth factor-binding protein ,Receptor, IGF Type 1 ,Cell membrane ,03 medical and health sciences ,Insulin-like growth factor ,0302 clinical medicine ,Somatomedins ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Receptor ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,biology ,Chemistry ,Somatomedin ,3. Good health ,Insulin-Like Growth Factor Binding Protein 2 ,Insulin-Like Growth Factor Binding Protein 3 ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,biology.protein ,Colorectal Neoplasms ,Oxidation-Reduction ,Protein Binding - Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and also the one with the highest mortality rate. Tumor growth is assisted by various growth factors, and insulin-like growth factors (IGFs) are among the most important. A majority of the IGFs are bound to IGF-binding proteins (IGFBPs) and their release is dependent on the rate of IGFBP proteolysis. The action of free IGFs is exerted and controlled by binding to cell membrane receptors (IGF-Rs). The objective of this work was to connect two determinants of the CRC pathology: oxidation as a process that underlies tumor development and the members of the IGF system that control it. Carbonyl groups (CO) on IGFBP-2, IGFBP-3, IGF-1R, and IGF-2R were determined in samples obtained from patients with CRC, and IGF-binding properties of these proteins were analyzed. According to our results, IGFBP-2 and IGFBP-3 in serum had increased content of CO groups due to CRC. Oxidation of IGFBP-2 increased its affinity for IGF molecules, whereas oxidation of IGFBP-3 reduced it. As for receptors, only intact CO-IGF-2R was detected on solubilized colon membranes, whereas CO-IGF-1R was degraded into fragments. Oxidative changes in the IGF axis may be regarded as part of the mechanism of its action. IGFs bound to IGFBP-3 remain in the circulation, whereas those bound to IGFBP-2 freely reach target tissues. Therefore, oxidation supports IGF distribution toward tissues and, consequently, promotes tumor growth.
- Published
- 2013
17. Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span
- Author
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Claudio Torres, Susan M. Motch, Christian Sell, Roger McCarter, Antonello Lorenzini, Adam B. Salmon, Yuji Ikeno, Chad A. Lerner, A. Lorenzini, A. B. Salmon, C. Lerner, C. Torre, Y. Ikeno, S. Motch, R. McCarter, and C. Sell
- Subjects
Aging ,medicine.medical_specialty ,Genotype ,medicine.medical_treatment ,media_common.quotation_subject ,Longevity ,Growth hormone receptor ,Biology ,Mice ,Insulin-like growth factor ,LIFE SPAN ,Internal medicine ,medicine ,Insulin ,Animals ,Obesity ,Insulin-Like Growth Factor I ,Receptor ,Maximum life span ,media_common ,Gene Expression Regulation, Developmental ,Somatomedin ,GH ,Mice, Inbred C57BL ,Metabolism ,Endocrinology ,Cohort ,IGF-1 ,Original Article ,Female ,Geriatrics and Gerontology ,Gluconeogenesi - Abstract
Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice.
- Published
- 2013
18. Monitoring for potential residual disease activity by serum insulin-like growth factor 1 and soluble Klotho in patients with acromegaly after pituitary surgery: Is there an impact of the genomic deletion of exon 3 in the growth hormone receptor (d3-GHR) gene on 'safe' GH cut-off values?
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René L. Bernays, Sibylle Kohler, Oliver Tschopp, Marian Christoph Neidert, Peter Wiesli, K S Spanaus, Lisa Sze, Christoph Schmid, University of Zurich, and Schmid, C
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Insulin-like growth factor 1 ,medicine.medical_specialty ,Monitoring ,medicine.medical_treatment ,10265 Clinic for Endocrinology and Diabetology ,610 Medicine & health ,Growth hormone receptor ,Disease ,Biology ,Insulin-like growth factor ,10180 Clinic for Neurosurgery ,Endocrinology ,Internal medicine ,Diagnosis ,Acromegaly ,540 Chemistry ,medicine ,Humans ,Insulin-Like Growth Factor I ,Klotho ,Klotho Proteins ,10038 Institute of Clinical Chemistry ,Glucuronidase ,Transsphenoidal surgery ,Growth factor ,Alpha-Klotho ,Exons ,Receptors, Somatotropin ,medicine.disease ,Somatomedin ,1310 Endocrinology ,Pituitary Gland ,Animal Science and Zoology ,1103 Animal Science and Zoology - Abstract
BackgroundAcromegaly is an illness usually defined by excessively high growth hormone (GH) and insulin like growth factor 1 (IGF-1) levels, the latter mainly reflecting GH action on the liver. IGF-1, also known as somatomedin C, mediates several actions of GH. The diagnosis and management of acromegaly is relatively straight forward, but long-term follow-up of patients can be difficult, as elevated IGF-1 levels can occur in the presence of apparently normalised GH levels and late recurrence of acromegaly may arise despite previous suppression on oral glucose tolerance testing. Data suggest this applies especially to patients in whom the GH receptor lacks exon 3. In such patients, GH may not always be a useful marker of disease, and traditional GH cut-offs may be misleading. Recent data suggest that soluble Klotho (sKlotho), besides and in addition to IGF-1, may help monitor the activity of GH-producing adenomas (presumably reflecting GH action on the kidneys) and may be a useful supplementary tool.MethodsGHR genotyping was performed in 112 patients with acromegaly. IGF-1 and sKlotho levels were measured in the sera of patients before and after transsphenoidal surgery, with emphasis on patients judged inconclusively cured by surgery or with small residual tumour masses shortly after surgery. Patients were assessed for recurrence of acromegaly with GH levels (random or nadir during an oGTT).ResultsOf the 48 patients who underwent surgery between 2000 and 2009 and who had well-documented longer term follow-up at our institution, 29 had no biochemical evidence of residual disease activity after transsphenoidal surgery (marked reduction in IGF-1 and sKlotho levels, GH suppressible to
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- 2013
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19. Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts
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Brandon Castor, Franck Calzone, Jonathan W. Said, David Elashoff, Ashley Gray, William J. Aronson, Colette Galet, Pedro J. Beltran, Junxiang Wan, and Pinchas Cohen
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Male ,Aging ,Antibodies, Neoplasm ,medicine.medical_treatment ,Somatomedin ,Mice, SCID ,Receptor, IGF Type 1 ,lcsh:Chemistry ,Prostate cancer ,Mice ,0302 clinical medicine ,Receptors ,Monoclonal ,Receptor ,Saline ,Humanized ,lcsh:QH301-705.5 ,Spectroscopy ,Cancer ,0303 health sciences ,Tumor ,Antibodies, Monoclonal ,IGF-1R blockade ,General Medicine ,calorie restriction ,prostate cancer ,3. Good health ,Computer Science Applications ,Neoplasm Proteins ,030220 oncology & carcinogenesis ,Heterografts ,Urologic Diseases ,medicine.medical_specialty ,Combination therapy ,Calorie restriction ,Antibodies, Monoclonal, Humanized ,SCID ,Article ,Catalysis ,Antibodies ,Cell Line ,Inorganic Chemistry ,03 medical and health sciences ,Clinical Research ,Cell Line, Tumor ,Internal medicine ,medicine ,Genetics ,Animals ,Humans ,IGF Type 1 ,Physical and Theoretical Chemistry ,Molecular Biology ,Protein kinase B ,Nutrition ,030304 developmental biology ,Caloric Restriction ,Chemical Physics ,business.industry ,Organic Chemistry ,Prostatic Neoplasms ,Receptors, Somatomedin ,medicine.disease ,Xenograft Model Antitumor Assays ,Blockade ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Apoptosis ,Neoplasm ,Other Biological Sciences ,business ,Other Chemical Sciences ,Neoplasm Transplantation - Abstract
Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.
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- 2013
20. Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin
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Michael A. Preece, Jennifer Jones, Barbara M. Ansell, Cecilia Camacho-Hübner, Jonathan Reeve, Ursula M. Davies, André Charlett, and Patricia Woo
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musculoskeletal diseases ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Osteocalcin ,IGFBP3 ,Insulin-like growth factor-binding protein ,Insulin-like growth factor ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,Pharmacology (medical) ,Insulin-Like Growth Factor I ,Child ,Analysis of Variance ,biology ,medicine.diagnostic_test ,Dose-Response Relationship, Drug ,business.industry ,Growth factor ,Insulin ,Somatomedin ,Arthritis, Juvenile ,Insulin-Like Growth Factor Binding Protein 1 ,Insulin-Like Growth Factor Binding Proteins ,Endocrinology ,Insulin-Like Growth Factor Binding Protein 3 ,Erythrocyte sedimentation rate ,Growth Hormone ,biology.protein ,Female ,business - Abstract
OBJECTIVE: To investigate possible mechanisms of growth impairment in children with juvenile rheumatoid arthritis (JRA). METHODS: Eighteen prepubertal children with JRA and growth retardation received recombinant human growth hormone (rHuGH) for 1 year. Growth hormone profiles over 24 hours were obtained before treatment in 12 patients; the levels did not differ from those in "short normal" children. Levels of insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs) 1 and 3, insulin, osteocalcin, and C-reactive protein (CRP), as well as the erythrocyte sedimentation rate were measured serially. Pretreatment levels were compared with control levels. RESULTS: In JRA patients, IGF-1, IGFBP-3, and osteocalcin levels were significantly lower and insulin levels significantly higher than those in controls, but there was no significant difference in the level of IGFBP-1. With rHuGH treatment, height velocity and mean levels of IGF-1, osteocalcin, and insulin increased significantly, while mean levels of IGFBP-1 fell significantly. Levels of IGFBP-3 correlated with those of IGF-1. The height velocity correlated positively with IGF-1 and osteocalcin, and negatively with IGFBP-1. Levels of IGFBP-1 were inversely related to those of insulin and IGF-1. There was a significant negative correlation between the CRP and height velocity, IGF-1 level, and osteocalcin level. CONCLUSION: IGF-1 production is impaired in children with active JRA. Treatment with a therapeutic dose of rHuGH can rectify the IGF-1 deficiency within 4 days, but its effect is adversely influenced by the acute-phase response, as reflected by an elevated CRP level.
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- 2016
21. Plasma somatomedin activity after injury in man and its relationship to other hormonal and metabolic changes
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D. A. Price, P. F. Maycock, K. N. Frayn, and S. M. Carroll
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,animal structures ,Time Factors ,Anabolism ,Adolescent ,Hydrocortisone ,Nitrogen ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Protein metabolism ,Excretion ,chemistry.chemical_compound ,Endocrinology ,Somatomedins ,Internal medicine ,medicine ,Humans ,Insulin ,Catabolism ,business.industry ,Middle Aged ,Somatomedin ,chemistry ,Growth Hormone ,Wounds and Injuries ,business ,hormones, hormone substitutes, and hormone antagonists ,Hormone ,medicine.drug - Abstract
Plasma somatomedin activity was measured in 12 patients who had sustained non-fatal musculo-skeletal injuries. It was depressed for 2-3 d after injury, but this depression bore no relationship to the catabolic response to injury which, as judged by urinary nitrogen excretion, was maximal at about one week. The depression of somatomedin activity may have been related to the high plasma cortisol concentrations observed during the first few days after injury. Plasma growth hormone concentrations were high acutely after injury but rapidly returned to normal. The changes in plasma somatomedin activity were thus unrelated to those in growth hormone, but were very similar to those in plasma insulin concentrations. A marked positive relationship was observed between plasma insulin concentrations and urinary nitrogen excretion, indicating unresponsiveness of protein metabolism to the normal anabolic effects of insulin. The study showed, however, that this was not as a result of low somatomedin activity.
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- 2016
22. Effect of the Quantity and Nutritional Quality of Dietary Proteins on the Transcriptional Activity of Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-1 Genes
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Shinichiro Takahashi, Yasunobu Uchijima, Tadashi Noguchi, and Yutaka Miura
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Transcriptional activity ,biology ,medicine.medical_treatment ,Binding protein ,Growth factor ,Organic Chemistry ,General Medicine ,Applied Microbiology and Biotechnology ,Biochemistry ,Somatomedin ,Insulin-like growth factor-binding protein ,Analytical Chemistry ,Insulin-like growth factor ,Transcription (biology) ,medicine ,biology.protein ,Molecular Biology ,Gene ,Biotechnology - Abstract
(1993). Effect of the Quantity and Nutritional Quality of Dietary Proteins on the Transcriptional Activity of Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-1 Genes. Bioscience, Biotechnology, and Biochemistry: Vol. 57, No. 2, pp. 358-359.
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- 2016
23. Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation
- Author
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Takashi Koyama and Christen K. Mirth
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0301 basic medicine ,Cell signaling ,Physiology ,medicine.medical_treatment ,Peptide ,Signal transduction ,Biochemistry ,Fats ,0302 clinical medicine ,Larvae ,Endocrinology ,Insulin Secretion ,Medicine and Health Sciences ,Post-Translational Modification ,Biology (General) ,chemistry.chemical_classification ,Signal peptides ,Insulin secretion ,General Neuroscience ,Drosophila Melanogaster ,Animal Models ,Somatomedin ,Lipids ,Amino acid ,Insects ,Drosophila melanogaster ,Physiological Parameters ,Drosophila ,General Agricultural and Biological Sciences ,Physiological parameters ,Signal Peptides ,Research Article ,medicine.medical_specialty ,Cell biology ,Arthropoda ,QH301-705.5 ,Biology ,Research and Analysis Methods ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Model Organisms ,Internal medicine ,medicine ,Animals ,Secretion ,TOR signaling ,Nutrition ,General Immunology and Microbiology ,Metamorphosis ,Biology and life sciences ,Endocrine Physiology ,Insulin ,Growth factor ,Organisms ,Proteins ,Invertebrates ,030104 developmental biology ,chemistry ,TOR Serine-Threonine Kinases ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size., The insect fat body transmits nutritional information to control body growth by producing and secreting two peptides, GBP1 and GBP2, in response to dietary amino acids. These two peptides stimulate insulin-like peptide secretion, increasing insulin-signaling activity throughout the body and inducing systemic growth., Author Summary Organisms adjust their development in response to environmental conditions to maximize important life history traits such as body size and survival. From work in the fruit fly, Drosophila melanogaster, we are beginning to resolve some of the molecular mechanisms through which environmental conditions, specifically nutrition, modify developmental processes. The insect fat body is functionally equivalent to the mammalian liver and adipocytes. In response to the concentration of dietary amino acids, the fat body secretes a peptide signal into the insect bloodstream that regulates the systemic release of important growth-regulating peptides, the insulin-like peptides. The nature of this peptide signal was previously unknown. Here we found that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids. Once secreted from the fat body, these two peptides stimulate secretion of insulin-like peptides, which results in elevating insulin-signaling activity in the rest of the body to stimulate body growth.
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- 2016
24. Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the Structure and Function of the Bovine Corpus Luteum
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Danila Barreiro Campos, Paula de Carvalho Papa, Gabriela P. Mendes, Pietro Sampaio Baruselli, and Liza Margareth Medeiros de Carvalho Sousa
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0301 basic medicine ,Physiology ,Gonadotropins, Equine ,medicine.medical_treatment ,Protein Expression ,Gene Expression ,lcsh:Medicine ,Cardiovascular Physiology ,Biochemistry ,Electrocardiography ,Endocrinology ,Animal Cells ,Medicine and Health Sciences ,Insulin ,Insulin-Like Growth Factor I ,lcsh:Science ,Progesterone ,Multidisciplinary ,biology ,Neurochemistry ,Somatomedin ,medicine.anatomical_structure ,Bioassays and Physiological Analysis ,Female ,Signal transduction ,Cellular Types ,Neurochemicals ,Corpus luteum ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Ovulation ,medicine.medical_specialty ,endocrine system ,Research and Analysis Methods ,Nitric Oxide ,03 medical and health sciences ,Corpus Luteum ,Internal medicine ,medicine ,Gene Expression and Vector Techniques ,Genetics ,Animals ,Equine chorionic gonadotropin ,Molecular Biology Techniques ,Molecular Biology ,Immunohistochemistry Techniques ,Diabetic Endocrinology ,Messenger RNA ,Molecular Biology Assays and Analysis Techniques ,Electrophysiological Techniques ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Hormones ,Histochemistry and Cytochemistry Techniques ,Insulin receptor ,030104 developmental biology ,Gene Expression Regulation ,CORPO LÚTEO ,biology.protein ,Immunologic Techniques ,Lutein Cells ,Cattle ,lcsh:Q ,Cardiac Electrophysiology ,Angiogenesis ,GLUT4 ,Developmental Biology ,Neuroscience - Abstract
We hypothesized that stimulatory and superovulatory treatments, using equine chorionic gonadotropin (eCG), modulate the expression of genes related to insulin, cellular modelling and angiogenesis signaling pathways in the bovine corpus luteum (CL). Therefore, we investigated: 1-the effect of these treatments on circulating insulin and somatomedin C concentrations and on gene and protein expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules; 2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9 and PLAU. Serum insulin did not differ among groups (P = 0.96). However, serum somatomedin C levels were higher in both stimulated and superovulated groups compared to the control (P = 0.01). In stimulated cows, lower expression of INSR mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In superovulated cows, lower INSR mRNA expression, but higher INSR protein expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were observed. Expression of angiogenesis and cellular modelling pathway-related factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9 gene and protein expression were lower in stimulated animals. In superovulated cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2 gene and protein expression were lower in both stimulated and superovulated animals related to the control. In vitro, eCG stimulated luteal cells P4 production as well as INSR and GLUT4 protein expression. In summary, our results suggest that superovulatory treatment induced ovarian proliferative changes accompanied by increased expression of genes providing the CL more energy substrate, whereas stimulatory treatment increased lipogenic activity, angiogenesis and plasticity of the extracellular matrix (ECM).
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- 2016
25. Insulin-Like Growth Factors in the Gastrointestinal Tract and Liver
- Author
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John F. Kuemmerle
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medicine.medical_specialty ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Apoptosis ,Inflammation ,Biology ,medicine.disease_cause ,Article ,Insulin-like growth factor-binding protein ,Receptor, IGF Type 1 ,Mice ,Endocrinology ,Somatomedins ,Internal medicine ,medicine ,Animals ,Humans ,Endocrine system ,Cell Proliferation ,Gastrointestinal Neoplasms ,Gastrointestinal tract ,Cell growth ,Insulin ,Somatomedin ,Rats ,Gastrointestinal Tract ,Insulin-Like Growth Factor Binding Proteins ,Liver ,biology.protein ,medicine.symptom ,Carcinogenesis - Abstract
The liver is a major source of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) that are present in the circulation and have important endocrine activities relating to energy metabolism, body size, carcinogenesis, and various organ-specific functions. Although IGFs have only minor effects on the normal liver itself, production of IGFs and IGFBPs in a tissue-specific manner in the gastrointestinal tract exert important regulatory effects on cellular proliferation, survival, and apoptosis. IGFs and IGFBPs play important regulatory roles in the response of both the liver and the gastrointestinal tract to inflammation and in the development of neoplasia.
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- 2012
26. Mapping the growth hormone–Stat5b–IGF-I transcriptional circuit
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Peter Rotwein
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medicine.medical_specialty ,animal structures ,Transcription, Genetic ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,STAT5B ,Biology ,medicine.disease_cause ,Models, Biological ,Article ,Endocrinology ,Mediator ,Transcription (biology) ,Internal medicine ,STAT5 Transcription Factor ,medicine ,Animals ,Humans ,Insulin-Like Growth Factor I ,Transcription factor ,Regulation of gene expression ,Growth factor ,Somatomedin ,Growth Hormone ,Carcinogenesis - Abstract
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert powerful influences on somatic growth, metabolism, and tissue repair, and have been implicated in aging and carcinogenesis. Since the formulation of the somatomedin hypothesis over 50 years ago, GH and IGF-I have been linked intimately to one another. Recent studies have established that GH potently stimulates IGF-I gene transcription, and through this mechanism controls production of IGF-I. A key mediator of the GH - IGF-I biosynthetic pathway is the latent transcription factor Stat5b. This review summarizes the potentially complex mechanistic relationship among GH action, Stat5b, and IGF-I gene activation, and suggests that Stat5b may have a broad role in mediating IGF-I gene regulation in response to diverse physiological inputs.
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- 2012
27. The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat
- Author
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Vera Gorbunova, Chris G. Faulkes, Michael Toft Overgaard, Cheryl A. Conover, and Malene Brohus
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Male ,Proteases ,medicine.medical_specialty ,Aging ,medicine.medical_treatment ,lcsh:Medicine ,Insulin-like growth factor ,Mice ,Species Specificity ,Somatomedins ,Internal medicine ,medicine ,Negligible senescence ,Animals ,Humans ,Pregnancy-Associated Plasma Protein-A ,lcsh:Science ,Receptor ,Gene ,Naked mole-rat ,Multidisciplinary ,Protease ,biology ,Mole Rats ,lcsh:R ,biology.organism_classification ,Somatomedin ,Cell biology ,Rats ,Endocrinology ,Insulin-Like Growth Factor Binding Protein 4 ,lcsh:Q ,Female ,Insulin-Like Growth Factor Binding Protein 5 ,Research Article - Abstract
Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process.
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- 2015
28. The IGF system
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Ezio Ghigo, Marta Annunziata, and Riccarda Granata
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Carbohydrate metabolism ,Biology ,Neuroprotection ,Receptor, IGF Type 1 ,Endocrinology ,Somatomedins ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,Insulin ,Receptor ,Cell Proliferation ,Cell growth ,Growth factor ,General Medicine ,Somatomedin ,Mitogens ,Signal transduction ,Signal Transduction - Abstract
The insulin-like growth factor (IGF) system plays essential role in the regulation of cell growth, proliferation and survival and affects nearly every organ system in the body. IGF-I, which has a high structural similarity to insulin, exerts growth-promoting effects, influences glucose metabolism and has neuroprotective and cardioprotective effects, partly because of its cell-proliferative and antiapoptotic properties. Aberrations in the IGF system may associate with various pathological conditions, including cancer. Insulin and its synthetic analogs are known to possess IGF-IR binding affinity, and concern has been raised about their mitogenic potential in humans. The present review summarizes the main aspects of the IGF system biology and the interactions among IGF-I, insulin, insulin analogs and their receptors.
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- 2010
29. Effects of Prenatal Ethanol Exposure on Postnatal Growth and the Insulin-Like Growth Factor Axis
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Germán Iñiguez, Christopher Cox, Mary Conley, James L. Mills, James Troendle, Fernando Cassorla, Sofía Aros, and Alejandra Avila
- Subjects
Leptin ,Male ,medicine.medical_specialty ,Alcohol Drinking ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Fetal alcohol syndrome ,Alcohol abuse ,Body Mass Index ,Insulin-like growth factor ,Child Development ,Endocrinology ,Insulin-Like Growth Factor II ,Pregnancy ,Somatomedins ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Insulin-Like Growth Factor I ,Growth Disorders ,Original Paper ,business.industry ,Growth factor ,Infant, Newborn ,Infant ,medicine.disease ,Somatomedin ,Fetal Alcohol Spectrum Disorders ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Infant, Small for Gestational Age ,Pediatrics, Perinatology and Child Health ,Small for gestational age ,Female ,business ,Biomarkers - Abstract
Aims: To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. Methods: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (≧48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. Results: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. Conclusion: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure.
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- 2010
30. Expression of insulin-like growth factor I messenger ribonucleic acid in regenerating bone after fracture: Influence of indomethacin
- Author
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Agneta Levinovitz, Per T. Prisell, Dan Edwall, Gunnar Norstedt, and E. Jennische
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Male ,medicine.medical_specialty ,Bone Regeneration ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Indomethacin ,Biology ,Insulin-like growth factor ,In vivo ,Internal medicine ,Gene expression ,medicine ,Animals ,Myocyte ,Orthopedics and Sports Medicine ,RNA, Messenger ,Tibia ,Bony Callus ,Insulin-Like Growth Factor I ,Growth factor ,Nucleic Acid Hybridization ,Rats, Inbred Strains ,Immunohistochemistry ,Somatomedin ,Rats ,Tibial Fractures ,Endocrinology ,Callus - Abstract
Expression of insulin-like growth factor I (IGF-I) was studied during time in the callus formed after tibial fracture in rats. Levels of IGF-I mRNA in callus peaked on the day 8 postfracture, showing a 10- to 15-fold induction compared to control bone. Levels of IGF-I mRNA tended also to be increased in the fracture-adjacent musculus tibialis anterior. IGF-I immunoreactivity was found in cartilaginous cells, osteoblasts, and myocytes 6 and 8 days after fracture. No obvious differences were found between hypophysectomized animals and control animals with regard to IGF-I immunoreactivity. Administration of the antiinflammatory drug indomethacin decreased the IGF-I mRNA expression in the tibial fracture model. Previous findings have shown that IGF-I is activated during in vivo muscle regeneration, and also in this model indomethacin administration reduces the expression of IGF-I. The finding that indomethacin administration reduces IGF-I expression could indicate that an inflammatory response may be important for activation of IGF-I during tissue regeneration.
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- 2009
31. A Fat Body-Derived IGF-like Peptide Regulates Postfeeding Growth in Drosophila
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Michael B. O'Connor, Yasuyoshi Nishida, Naoki Okamoto, Naoki Yamanaka, Akira Mizoguchi, Hiroshi Kataoka, and Yoshimasa Yagi
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medicine.medical_specialty ,medicine.medical_treatment ,Fat Body ,Mutant ,DEVBIO ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Somatomedins ,Internal medicine ,Drosophilidae ,medicine ,Animals ,Body Size ,Drosophila Proteins ,Molecular Biology ,Ecdysteroid ,Growth factor ,Ecdysteroids ,Cell Biology ,biology.organism_classification ,Phenotype ,Somatomedin ,Drosophila melanogaster ,Endocrinology ,chemistry ,Mutation ,Drosophila Protein ,Developmental Biology - Abstract
SummaryMembers of the insulin family of peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Here we show that Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to vertebrate insulin-like growth factor (IGF), is predominantly expressed in the fat body, a functional equivalent of the vertebrate liver and adipocytes. This expression occurs during the postfeeding stage under the direct regulation of ecdysteroid. We further reveal that dilp6 mutants show growth defects during the postfeeding stage, which results in reduced adult body size through a decrease in cell number. This phenotype is rescued by fat body-specific expression of dilp6. These data indicate that DILP6 is a functional, as well as a structural, counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of ILPs in determining adult body size through the regulation of postfeeding growth.
- Published
- 2009
32. Effect of Endurance Exercise on Somatomedin- C/lnsulin-like Growth Factor I Concentration in Male and Female Runners*)
- Author
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V Hesse, H E Schmidt, G. Jahreis, and J Scheibe
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Running ,Insulin-like growth factor ,Sex Factors ,Endocrinology ,Somatomedins ,Stress, Physiological ,Endurance training ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Young female ,Energy deficiency ,business.industry ,General Medicine ,Somatomedin ,Prolactin ,Carrier protein ,Physical Endurance ,Female ,business ,Hormone - Abstract
By means of 3 endurance exercises, the effect of a several-hour intensive somatic stress on the changes of the Sm-C/IGF-I concentration was tested during, immediately after and on the day following the exercise. Exp. 1: Marathon with 17 male sportsmen in 2 groups with different glucose supply. Exp. 2: 45-km crosscountry run with 41 males. Exp. 3: Three 20-km runs with 8 young females at intervals of 3 months. In the marathon, no significant changes of the Sm-C/IGF-I concentration were found between the start, half distance and final values. The exogenous glucose supply (continuous or discontinuous) had also no effect. The tendency of a slight decrease of the Sm-C/IGF-I concentration by 0.14 U/ml (p greater than 0.05) was observed between start and finish in the 45 km crosscountry run lasting one hour longer. In the three 20-km runs, reproducible, slightly increased levels were measured at the end, whereas a decrease to the initial value or even below was detected on the following day (p greater than 0.05). The insignificant alterations of the Sm-C/IGF-I concentration measured in the 3 variants of races show that neither the hormonal changes stimulating the Sm-C/IGF-I synthesis (e.g. increase of GH and prolactin) nor inhibiting factors (energy deficiency) clearly dominate during strenuous exercises. The binding of carrier protein prevents great variations of the Sm-C/IGF-I level even under the condition of 3- to 4-hour extreme endurance exercises.
- Published
- 2009
33. Somatomedin-C in Active and Successfully Treated Acromegaly
- Author
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G. Knappe, V. Hesse, W. Rohde, Helga Gerl, and G. Jahreis
- Subjects
medicine.medical_specialty ,Chemotherapy ,Diagnostic methods ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,General Medicine ,medicine.disease ,Somatomedin ,Growth hormone secretion ,Elevated serum ,Endocrinology ,Internal medicine ,Acromegaly ,Internal Medicine ,medicine ,business ,Normal range - Abstract
Sm-C concentrations in serum were found significantly different in either active acromegaly or following successful treatment with pituitary adenomectomy. Although after normalization of serum GH the Sm-C levels sometimes exceeded the normal range no overlap was found between both groups. Exceptionally two acromegalic patients showed elevated Sm-C levels in spite of normal GH values. Likewise, a high Sm-C concentration was found in one patient suspective of ectopic GH secretion with only moderately elevated serum GH. Sm-C determinations are judged as a good adjunct to usual diagnostic methods which in special cases of acromegaly can be even superior to measurements of serum GH.
- Published
- 2009
34. Somatomedin-C/IGF-I, Insulin and Prolactin Levels in Ullrich-Turner's Syndrome
- Author
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P. Amendt, W. Rohde, and V. Hesse
- Subjects
medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Radioimmunoassay ,Turner Syndrome ,Biology ,Pathogenesis ,Basal (phylogenetics) ,Endocrinology ,Internal medicine ,Turner syndrome ,Internal Medicine ,medicine ,Humans ,Insulin ,Insulin-Like Growth Factor I ,Child ,Pancreatic hormone ,Infant ,General Medicine ,medicine.disease ,Somatomedin ,Prolactin ,Sex steroid ,Child, Preschool ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
To clarify the pathogenesis of growth retardation in patients with Ullrich-Turner's syndrome (TS) we have investigated basal SmC/IGF-I, insulin and prolactin concentrations. Compared with 56 age matched healthy controls basal SmC/IGF-I concentration in 51 patients with TS older than 9-11 years was significantly lower (age group 13-14 years; TS 273 +/- 47 and controls 479 +/- 114 ng/ml). Mean basal prolactin level in 43 patients with TS (406 +/- 211 microU/ml) was significantly higher (p less than 0.01) than in 192 female controls (age 3-11 years; 264 +/- 176 microU/ml). Basal insulin concentration in 28 TS patients in comparison to 20 healthy children of a control group was significant higher (TS 18 +/- 8 microU/ml; controls 9 +/- 4 microU/ml; p less than 0.01). It seems that neither insulin nor prolactin are relevant stimulators of Smc/IGF-I in man, especially in patients with gonadal dysgenesis. Considering these results we speculate that despite higher prolactin and higher insulin levels in TS, the lower SmC/IGF-I concentrations may be predominantly related to the abnormal sex steroid secretion.
- Published
- 2009
35. Effect of 24-Hour Somatostatin Infusion on Glucose Homeostasis and on the Levels of Somatomedin A and Pancreatic and Thyroid Hormones in Man
- Author
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Suad Efendic, Kerstin Hall, and P. E. Lins
- Subjects
Adult ,Blood Glucose ,Male ,Thyroid Hormones ,endocrine system ,medicine.medical_specialty ,Triiodothyronine, Reverse ,medicine.medical_treatment ,Thyrotropin ,Glucagon ,Bolus (medicine) ,Somatomedins ,Internal medicine ,Internal Medicine ,Homeostasis ,Humans ,Insulin ,Medicine ,Glucose homeostasis ,Infusions, Parenteral ,Triiodothyronine ,business.industry ,Thyroid ,Middle Aged ,Somatomedin ,Thyroxine ,Somatostatin ,medicine.anatomical_structure ,Endocrinology ,Growth Hormone ,Female ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
In order to investigate whether somatostatin plays a role in the regulation of thyroid hormone secretion we have compared the effects of a prolonged somatostatin infusion on insulin and glucagon levels, on the one hand, with its effect on T4, T3, rT3 and TSH, on the other. Furthermore, the serum levels of somatomedin A were determined. Saline was infused in control experiments. Cyclic somatostatin was given as an i.v. bolus of 200 micrograms followed by a constant rate infusion of 50 micrograms/h during 24 hours. Somatostatin suppressed basal insulin and glucagon levels as well as insulin responses to meals but did not influence somatomedin A levels. T4 and T3 decreased during the first hour, whether somatostatin was given or not. Thereafter, T4 and T3 remained stable in the control experiments, while they continued to decrease slowly when somatostatin was added. The suppressive effect of somatostatin was significant 11 hours (p less than 0.05) and 24 hours (p less than 0.005) after the onset of the infusion. In contrast, rT3 and TSH were not suppressed by somatostatin. The fact that basal TSH did not decrease, favors the idea that the suppression of T4 and T3 was mainly due to a direct inhibitory effect of somatostatin on the thyroid gland. Our observation that a low dose of somatostatin decreases peripheral T4 and T3 levels supports the idea that somatostatin plays a role in the regulation of thyroid hormone secretion.
- Published
- 2009
36. Insulin signaling pathways and cardiac growth
- Author
-
Anthony J. Muslin and Brian J. DeBosch
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Biology ,Article ,Somatomedins ,Diabetic cardiomyopathy ,Internal medicine ,medicine ,Extracellular ,Animals ,Humans ,Insulin ,Receptor ,Molecular Biology ,Heart ,medicine.disease ,Somatomedin ,Receptor, Insulin ,Insulin receptor ,Endocrinology ,Heart failure ,biology.protein ,Signal transduction ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
The development, growth, function and metabolism of the heart are regulated by extracellular growth factors, cytokines and ligands. In this review, the role of insulin and insulin-like growth factors in the regulation of cardiac growth will be discussed. In addition, the role of insulin- and insulin-like growth factor-stimulated intracellular signaling proteins in cardiac growth will be reviewed.
- Published
- 2008
37. Keine Verbesserung der Gelenkknorpelheilung nach Trauma durch intraarticuläre Gabe von insulinartigem Wachstumsfaktor I, epidermalem Wachstumsfaktor und Fibroblasten-Wachstumsfaktor beim Kaninchen
- Author
-
J. J. Neidel
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,business.industry ,Cartilage ,Growth factor ,medicine.medical_treatment ,Cell cycle ,Fibroblast growth factor ,Somatomedin ,Chondrocyte ,medicine.anatomical_structure ,Endocrinology ,In vivo ,Epidermal growth factor ,Internal medicine ,medicine ,Orthopedics and Sports Medicine ,Surgery ,business - Abstract
Insulin-like growth factor I (Somatomedin C), epidermal growth factor, and fibroblast growth factor exert a stimulatory effect on articular chondrocyte metabolism in vitro. We studied the effect of these peptides on the repair of standardized full-thickness articular cartilage defects in the knee-joints of 32 young adult rabbits. In our in vivo study, the growth factors failed to stimulate cartilage cell replication, chondrocyte proteoglycan synthesis or defect filling. The trauma, however, had a significant stimulatory effect on the mitotic activity of the chondrocytes near the defect, but not on the synthesis of sulfated proteoglycans.
- Published
- 2008
38. Structural Basis for the Lower Affinity of the Insulin-like Growth Factors for the Insulin Receptor
- Author
-
Lisbeth Gauguin, Briony E. Forbes, Birgit Klaproth, Kerrie A. McNeil, Asser Sloth Andersen, Waseem Sajid, and Pierre De Meyts
- Subjects
Models, Molecular ,medicine.medical_specialty ,medicine.medical_treatment ,Molecular Sequence Data ,In Vitro Techniques ,Binding, Competitive ,Biochemistry ,Cell Line ,Insulin-Like Growth Factor II ,Somatomedins ,Insulin receptor substrate ,Internal medicine ,medicine ,Animals ,Humans ,Insulin ,Amino Acid Sequence ,Insulin-Like Growth Factor I ,Protein Precursors ,Receptor ,Molecular Biology ,Peptide sequence ,chemistry.chemical_classification ,Sequence Homology, Amino Acid ,biology ,Growth factor ,Cell Biology ,Somatomedin ,Receptor, Insulin ,Protein Structure, Tertiary ,Rats ,Amino acid ,Kinetics ,Insulin receptor ,Endocrinology ,Amino Acid Substitution ,chemistry ,biology.protein - Abstract
Insulin and the insulin-like growth factors (IGFs) bind with high affinity to their cognate receptor and with lower affinity to the noncognate receptor. The major structural difference between insulin and the IGFs is that the IGFs are single chain polypeptides containing A-, B-, C-, and D-domains, whereas the insulin molecule contains separate A- and B-chains. The C-domain of IGF-I is critical for high affinity binding to the insulin-like growth factor I receptor, and lack of a C-domain largely explains the low affinity of insulin for the insulin-like growth factor I receptor. It is less clear why the IGFs have lower affinity for the insulin receptor. In this study, 24 insulin analogues and four IGF analogues were expressed and analyzed to explore the role of amino acid differences in the A- and B-domains between insulin and the IGFs in binding affinity for the insulin receptor. Using the information obtained from single substituted analogues, four multiple substituted analogues were produced. A "quadruple insulin" analogue ([Phe(A8), Ser(A10), Thr(B5), Gln(B16)]Ins) showed affinity as IGF-I for the insulin receptor, and a "sextuple insulin" analogue ([Phe(A8), Ser(A10), Thr(A18), Thr(B5), Thr(B14), Gln(B16)]Ins) showed an affinity close to that of IGF-II for the insulin receptor, whereas a "quadruple IGF-I" analogue ([His(4), Tyr(15), Thr(49), Ile(51)]IGF-I) and a "sextuple IGF-II" analogue ([His(7), Ala(16), Tyr(18), Thr(48), Ile(50), Asn(58)]IGF-II) showed affinities similar to that of insulin for the insulin receptor. The mitogenic potency of these analogues correlated well with the binding properties. Thus, a small number of A- and B-domain substitutions that map to the IGF surface equivalent to the classical binding surface of insulin weaken two hotspots that bind to the insulin receptor site 1.
- Published
- 2008
39. Interaction between glucocorticoids and growth hormone
- Author
-
J. Schurek, Jun Oh, Catherine A. Mayer, Otto Mehls, G. Kovacs, and Burkhard Tönshoff
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Growth ,Biology ,Weight Gain ,Growth hormone ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Animals ,Humans ,Insulin-Like Growth Factor I ,Glucocorticoids ,Clinical Trials as Topic ,Dose-Response Relationship, Drug ,Growth factor ,Receptors, Somatotropin ,General Medicine ,Somatomedin ,Rats ,Steroid hormone ,Endocrinology ,Cytokine ,Growth Hormone ,Pediatrics, Perinatology and Child Health ,Drug Therapy, Combination ,Female ,Glucocorticoid ,medicine.drug - Published
- 2008
40. Increasing dietary crude protein does not increase the methionine requirement in kittens
- Author
-
Quinton R. Rogers, Philip H. Kass, M. J. Strieker, and James G. Morris
- Subjects
Male ,medicine.medical_specialty ,Nitrogen balance ,Nitrogen ,Animal feed ,medicine.medical_treatment ,Cystine ,Weight Gain ,Random Allocation ,chemistry.chemical_compound ,Methionine ,Animal science ,Food Animals ,Latin square ,Internal medicine ,medicine ,Animals ,Dose-Response Relationship, Drug ,Insulin ,Nutritional Requirements ,Animal Feed ,Somatomedin ,Dose–response relationship ,Endocrinology ,Animals, Newborn ,chemistry ,Cats ,Animal Nutritional Physiological Phenomena ,Animal Science and Zoology ,Dietary Proteins - Abstract
The objective of this study was to determine if the methionine (met) requirement of kittens is correlated with the concentration of dietary crude protein (CP). The study used 48 male kittens in two replications of six 4 x 4 Latin squares, each representing one concentration of met (1.5, 2.5, 3.5, 4.5, 6.0 or 9.0 g/kg diet) with four CP concentrations (150, 200, 300 and 500 g/kg diet) in 2-week periods. Cystine was present in the lowest CP diet at 5.3 g/kg diet and increased as dietary CP increased. Body weight gain, food intake, nitrogen balance and plasma amino acids, glucose, insulin, cortisol, somatomedin C, T(3) and T(4) concentrations on day 12 were measured. From breakpoint analysis of the nitrogen retention curves, the met requirement of kittens was found to be 3.1, 3.8, 3.1 and 2.4 g met/kg for the 150, 200, 300 and 500 g CP/kg diets, respectively. When met was limiting (1.5 or 2.5 g/kg diet), increasing dietary CP did not decrease, but rather increased food intake, body weight gain and nitrogen retention. Plasma met concentrations increased as dietary met increased and at 2.5-3.5 g met/kg diet were not different among kittens fed the various CP diets. Total plasma T(3) and T(4) increased significantly as dietary CP increased in kittens given the 2.5 and 4.5 g met/kg diets. Results indicate that food intake and possibly altered hormonal secretion play a role in this growth response. In conclusion, the met requirement of growing kittens, unlike omnivores and herbivores studied, was not positively correlated with the concentration of dietary CP.
- Published
- 2007
41. Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep
- Author
-
Penelope A. Dalitz, Julie A. Owens, Megan L Cock, Kathryn L. Gatford, and Richard Harding
- Subjects
medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Glucose uptake ,Complement factor I ,Insulin-like growth factor-binding protein ,Insulin-like growth factor ,Insulin-Like Growth Factor II ,Pregnancy ,Somatomedins ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Insulin-Like Growth Factor I ,Maternal-Fetal Exchange ,Fetus ,Fetal Growth Retardation ,Sheep ,Ethanol ,biology ,Fetal Blood ,medicine.disease ,Somatomedin ,Insulin-Like Growth Factor Binding Proteins ,Endocrinology ,Fetal Weight ,embryonic structures ,biology.protein ,Pregnancy, Animal ,Gestation ,Female - Abstract
Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (−35%) at 30 h, and decreased fetal plasma IGF-II (−28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.
- Published
- 2007
42. Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes
- Author
-
Jan Frystyk, Mari-Anne Pulkkinen, Zhulin Ma, Peter Bang, Anna Lena Brorsson, Christine Carlsson-Skwirut, and Klas Ekström
- Subjects
Adult ,Blood Glucose ,Male ,Microdialysis ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Subcutaneous Fat ,030209 endocrinology & metabolism ,Context (language use) ,Biochemistry ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Hyperinsulinemia ,Humans ,Single-Blind Method ,Insulin-Like Growth Factor I ,030304 developmental biology ,Mecasermin ,0303 health sciences ,Type 1 diabetes ,Cross-Over Studies ,business.industry ,Insulin ,Muscles ,Biochemistry (medical) ,Glucose clamp technique ,medicine.disease ,Somatomedin ,Recombinant Proteins ,Diabetes Mellitus, Type 1 ,Glucose ,Glucose Clamp Technique ,business ,medicine.drug - Abstract
CONTEXT: Type 1 diabetes is associated with portal insulin deficiency and disturbances in the GH-IGF axis including low circulating IGF-I and GH hypersecretion. Whether peripheral hyperinsulinemia and GH hypersecretion, which are relevant to the development of vascular complications, result in elevated tissue IGF-I remains unknown.OBJECTIVE: The purpose of this study was to determine the relationship between whole-body glucose uptake and tissue IGF-I measured by microdialysis.DESIGN: This was a single-blind placebo-controlled crossover study.SETTING: The setting was a tertiary pediatric endocrine referral center.PARTICIPANTS: The participants were seven young male adults with type 1 diabetes.INTERVENTION: After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5 mU/kg × minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120 μg/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I).MAIN OUTCOME MEASURES: md-IGF-I levels in muscle and subcutaneous fat, and GIR were determined.RESULTS: md-IGF-I levels were detectable but unchanged after saline. After rhIGF-I, muscle and subcutaneous fat md-IGF-I increased during the second and third hour and then reached a plateau up to 10-fold higher than baseline (P < .001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P < .0001). In contrast, serum IGF-I was increased already at 30 minutes after rhIGF-I and reached a plateau 2-fold above baseline (P < .0001).CONCLUSION: We demonstrate that md-IGF-I measurements are valid and physiologically relevant by reflecting rhIGF-I-induced glucose uptake. Future studies should be conducted to elucidate the role of local tissue IGF-I in diabetic vascular complications.
- Published
- 2015
43. Renal Glomerular and Tubular Insulin and Insulin-Like Growth Factor Receptors
- Author
-
Elias Meezan and Dennis J. Pillion
- Subjects
medicine.medical_specialty ,Kidney ,business.industry ,Insulin ,medicine.medical_treatment ,Kidney Glomerulus ,Insulin-Like Growth Factor Receptor ,Somatomedin ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Medicine ,business ,Renal stem cell ,Kidney tubules - Published
- 2015
44. Epigenetic regulation of insulin-like growth factor signaling: A novel insight into the pathophysiology of neonatal pulmonary hypertension
- Author
-
Raffaele De Caterina, Rosalinda Madonna, and Yong-Jian Geng
- Subjects
Neonatal pulmonary arterial hypertension ,Physiology ,medicine.medical_treatment ,Somatomedin ,Pulmonary Artery ,Persistent Fetal Circulation Syndrome ,Epigenesis, Genetic ,Receptor, IGF Type 1 ,Hypoxemia ,Pathogenesis ,Insulin-like growth factor ,Genetic ,medicine.artery ,Receptors ,medicine ,Animals ,Humans ,Arterial Pressure ,Genetic Predisposition to Disease ,Insulin-Like Growth Factor I ,Pharmacology ,business.industry ,Insulin ,Infant, Newborn ,Infant ,Receptors, Somatomedin ,Epigenetics ,IGF-1 ,Insulin growth factor ,Newborn ,Phenotype ,Prognosis ,Signal Transduction ,Vascular Resistance ,medicine.anatomical_structure ,Blood pressure ,Pulmonary artery ,Immunology ,Vascular resistance ,Molecular Medicine ,medicine.symptom ,business ,Epigenesis - Abstract
Burdened by high morbidity and mortality, neonatal pulmonary hypertension (PH) is a life-threatening pathophysiological condition that progressively elevates the mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Pulmonary vascular remodeling and vasoconstriction are recognized pathophysiological features of the disease. Neonatal PH is a serious pathological condition in which persistent PH of the newborn causes hypoxemia and right-to-left extrapulmonary shunting of blood flow, leading to right heart failure and serious life-threatening complications. Recently, the role of growth factors in the pathogenesis of neonatal PH has attracted much attention. Here we provide an update on the ongoing research regarding the epigenetic regulation of the insulin growth factor (IGF)-1/IGF-1 receptor pathway, with insight into the potential regulatory role such regulation in the pathogenesis of neonatal PH.
- Published
- 2015
45. Evaluation of the Components of the Insulin-like Growth Factors System in GH-deficient Adults: Effects of Twelve-month rhGH Treatment
- Author
-
Emanuele Ferrante, S. Porretti, Andrea Lania, E. Vassallo, Cristina L. Ronchi, Anna Spada, Paolo Beck-Peccoz, and Claudia Giavoli
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Rhgh treatment ,Biochemistry ,Body Mass Index ,Endocrinology ,Insulin-Like Growth Factor II ,Somatomedins ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Normal range ,Glycoproteins ,Anthropometry ,Human Growth Hormone ,business.industry ,Insulin ,Biochemistry (medical) ,General Medicine ,Middle Aged ,Somatomedin ,Recombinant Proteins ,Insulin-Like Growth Factor Binding Protein 3 ,Stimulation tests ,Female ,Carrier Proteins ,business ,Body mass index ,GH Deficiency - Abstract
The impact of GH deficiency and rhGH replacement therapy on IGF-I, IGFBP-3 and ALS levels has been widely studied. There is less information available on IGF-II levels, the component of the ternary complex poorly dependent on GH. We investigate the components of IGFs system in 36 GHD adults (28M, 8F, age 45 +/- 14 yrs) before and after 12 months of rhGH therapy (mean dose 0.3 +/- 0.1 mg/day). One-hundred healthy sex- and age-matched subjects were studied for comparison. At baseline, GHD patients showed IGF-I and IGF-II levels and IGFs to IGFBP-3 molar ratios that were lower than controls. During therapy, IGF-I levels increased (p < 0.01) to normal range. IGF-II levels, though higher than at baseline (p < 0.01), remained lower than in controls (p < 0.01). ALS and IGFBP-3 significantly increased (p < 0.001). These modifications resulted in normalization in IGF-I to IGFBP-3 ratio, while no change in IGF-II to IGFBP-3 ratio was observed. In conclusion, the increase of serum IGF-II levels during rhGH treatment in GHD patients probably reflects the increase in the other components of ternary complex (ALS and IGFBP-3). However, serum IGF-II levels as well as IGF-II to IGFBP-3 ratio, although increased, were definitely lower than in controls. This last result, given the increasing evidences of a direct implication of IGF-II in cancer, may further confirm the safety of rhGH replacement in adults with severe GHD as diagnosed by appropriate stimulation tests.
- Published
- 2006
46. Effects of acute hypoxemia on insulin-like growth factors and their binding proteins in fetal sheep
- Author
-
S. D. Chernausek, H. S. Iwamoto, and Mary Murray
- Subjects
medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Endocrinology, Diabetes and Metabolism ,Immunoblotting ,Biology ,Insulin-like growth factor-binding protein ,Hypoxemia ,Fetus ,Pregnancy ,Somatomedins ,Internal medicine ,Physiology (medical) ,medicine ,Animals ,Insulin-Like Growth Factor I ,Hypoxia ,Sheep ,Insulin ,Growth factor ,Embryogenesis ,Osmolar Concentration ,Fetal Blood ,Somatomedin ,Insulin-Like Growth Factor Binding Proteins ,Molecular Weight ,Endocrinology ,Insulin-like growth factor 2 ,Acute Disease ,embryonic structures ,biology.protein ,Female ,Gases ,medicine.symptom ,Carrier Proteins - Abstract
It has been proposed that insulin-like growth factor I (IGF-I) regulates fetal growth and differentiation. Plasma IGF-I concentrations correlate positively with fetal nutrient availability and newborn birth weights. To explore the hypothesis that hypoxemia decreases fetal growth by decreasing fetal IGF-I availability, we instrumented 14 fetal sheep with vascular catheters. At least 4 days after surgery, 10 fetuses were made acutely hypoxemic by infusing nitrogen into the maternal trachea for 3 h. Fetal blood oxyhemoglobin saturation decreased from 53 +/- 6 (SD) to 31 +/- 9%. Concomitantly, plasma IGF-I concentrations decreased from 91 +/- 11 to 67 +/- 10 ng/ml and IGF-I binding protein-1 concentration increased significantly, as assessed by ligand and Western blot analysis. Fetal IGF-I concentrations remained below control values throughout a subsequent recovery period (68 +/- 12 ng/ml at 6 h). In four control fetuses and in the ewes, plasma IGF-I concentrations were not significantly different from control values (97 +/- 18 and 181 +/- 18 ng/ml, respectively). These data support the hypothesis that decreases in fetal oxygen availability may decrease fetal growth by decreasing IGF-I production and availability.
- Published
- 2006
47. Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes
- Author
-
Yanyan Qi, Pankaj Kapahi, Susan A. Jackson, Debamita Chatterjee, Subhash D. Katewa, and Heinrich Jasper
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Fat Body ,Molecular Sequence Data ,Somatomedins ,Internal medicine ,Ectoderm ,medicine ,Endocrine system ,Animals ,Drosophila Proteins ,Insulin ,Multidisciplinary ,Microscopy, Confocal ,biology ,Base Sequence ,Sequence Analysis, RNA ,Lipid Mobilization ,Metabolism ,Fasting ,Biological Sciences ,Somatomedin ,Adaptation, Physiological ,Insulin receptor ,Endocrinology ,biology.protein ,Drosophila ,Adaptation ,Drosophila Protein ,Homeostasis ,Metabolic Networks and Pathways - Abstract
Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liver-like oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulin-like peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance.
- Published
- 2014
48. Effects of L-carnitine on fetal growth and the IGF system in pigs1,2
- Author
-
J.P. Kayser, J. C. Woodworth, Bradley J. Johnson, A.T. Waylan, J. D. Starkey, James J. Higgins, D.P. Gnad, and E. K. Sissom
- Subjects
medicine.medical_specialty ,Fetus ,medicine.medical_treatment ,Uterus ,Uterine horns ,General Medicine ,Biology ,Somatomedin ,Insulin-like growth factor ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,Placenta ,Genetics ,medicine ,Gestation ,Animal Science and Zoology ,Carnitine ,Food Science ,medicine.drug - Abstract
The effects of L-carnitine on porcine fetal growth traits and the IGF system were determined. Fourth-parity sows were fed a gestation diet with either a 50-g top dress containing 0 (control, n = 6) or 100 mg of L-carnitine (n = 6). At midgestation, fetuses were removed for growth measurements, and porcine embryonic myoblasts (PEM) were isolated from semitendinosus. Real-time quantitative PCR was used to measure growth factor messenger RNA (mRNA) levels in the uterus, placenta, muscle, hepatic tissue, and cultured PEM. A treatment x day interaction (P = 0.02) was observed for maternal circulating total carnitine. Sows fed L-carnitine had a greater (P = 0.01) concentration of total carnitine at d 57 than control sows. Circulating IGF-I was not affected (P = 0.55) by treatment. Supplementing sows with L-carnitine resulted in larger (P = 0.02) litters (15.5 vs. 10.8 fetuses) without affecting litter weight (P = 0.07; 1,449.6 vs. 989.4 g) or individual fetal weight (P = 0.88) compared with controls. No treatment effect was found for muscle IGF-I (P = 0.36), IGF-II (P = 0.51), IGFBP-3 (P = 0.70), or IGFBP-5 (P = 0.51) mRNA abundance. The abundance of IGF-I (P = 0.72), IGF-II (P = 0.34), and IGFBP-3 (P = 0.99) in hepatic tissue was not influenced by treatment. Uterine IGF-I (P = 0.46), IGF-II (P = 0.40), IGFBP-3 (P = 0.29), and IGFBP-5 (P = 0.35) mRNA abundance did not differ between treatments. Placental IGF-I (P = 0.30), IGF-II (P = 0.18), IGFBP-3 (P = 0.94), and IGFBP-5 (P = 0.42) mRNA abundance did not differ between treatments. There was an effect of side of the uterus for IGF-I (P = 0.04) and IGF-II (P = 0.007) mRNA abundance; IGF-I mRNA abundance was greater in the left uterine horn than in the right uterine horn (0.14 and 0.07 relative units, respectively). Placental IGF-II mRNA abundance was greater (P = 0.007) in the left than in the right uterine horn (483.5 and 219.59, respectively). The abundance of IGFBP-3 was not affected by uterine horns in either uterine (P = 0.66) or placental (P = 0.13) tissue. There was no treatment difference for IGF-I (P = 0.31) or IGFBP-5 (P = 0.13) in PEM. The PEM isolated from sows fed L-carnitine had decreased IGF-II (P = 0.02), IGFBP-3 (P = 0.03), and myogenin (P = 0.04; 61, 59, and 67%, respectively) mRNA abundance compared with controls. These data suggest that L-carnitine supplemented to gestating sows altered the IGF system and may affect fetal growth and development.
- Published
- 2005
49. The growth hormone axis and insulin-like growth factors
- Author
-
Vera Todorović, Branka Šikić, Danijela Vucevic, and Tatjana Radosavljević
- Subjects
medicine.medical_specialty ,Mutation ,business.industry ,Growth factor ,medicine.medical_treatment ,Growth ,General Medicine ,medicine.disease_cause ,Somatomedin ,Paracrine signalling ,Endocrinology ,Somatomedins ,Growth Hormone ,Internal medicine ,medicine ,Animals ,Humans ,Endocrine system ,Growth factor receptor inhibitor ,Carcinogenesis ,Autocrine signalling ,business - Abstract
Introduction Growth is regulated by the interaction of environmental signals with endogenous neuroendocrine responses to the genetic programs that determine the body plan. The insulin-like growth factors (IGFs) are integral components of multiple systems controlling both growth and metabolism. The IGF system The IGF system is thought to be more complex than other endocrine systems, as genes for six IGF-binding proteins (IGFBPs) have been identified so far. The IGFs play a critical role in both cell cycle control and apoptosis, two functions involved in regulation of tumorigenesis. Insulin-like growth factor-I (IGF-I) is essential for normal growth. Confirmation of the significance of IGF-I in human physiology was obtained by the discovery of a patient with intrauterine growth retardation and postnatal growth failure associated with a mutation in the IGF-1 gene. Stages of evolution of the somatomedin hypothesis The original somatomedin hypothesis postulated that somatic growth was regulated by growth hormone's (GH's) stimulation of hepatic IGF-1 production, with IGF-1 acting in an endocrine fashion to promote growth. The dual effectors theory proposed an alternative view, involving direct effects by GH on peripheral tissues not mediated by IGF-1 and GH-stimulated local IGF-1 production for autocrine/paracrine action. It is now clear that G H stimulates the formation of ternary IGF binding complex, which stabilizes IGF-I in the serum.
- Published
- 2005
50. Effects of insulin--like growth factor-I treatment on the endocrine pancreas of hypophysectomized rats: comparison with growth hormone replacement
- Author
-
Jürgen Zapf, Evangelos Zoidis, Tanja Jevdjovic, Caroline Maake, Manfred Reinecke, Elisabeth Eppler, University of Zurich, and Zapf, J
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,10017 Institute of Anatomy ,Pituitary Diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Fluorescent Antibody Technique ,610 Medicine & health ,Biology ,Glucagon ,Islets of Langerhans ,Insulin-like growth factor ,Endocrinology ,Internal medicine ,medicine ,Animals ,Insulin ,Endocrine system ,RNA, Messenger ,Insulin-Like Growth Factor I ,Rats, Wistar ,Hypophysectomy ,C-Peptide ,Body Weight ,Organ Size ,General Medicine ,Somatomedin ,Rats ,1310 Endocrinology ,Insulin oscillation ,2712 Endocrinology, Diabetes and Metabolism ,medicine.anatomical_structure ,Growth Hormone ,570 Life sciences ,biology ,Pancreas ,Hormone - Abstract
Background: In GH-deficient humans, GH and IGF-I treatment cause opposite effects on serum insulin concentrations and insulin sensitivity. This finding contrasts with the somatomedin hypothesis that IGF-I mediates GH action, as postulated for skeletal growth, and raises the question whether GHinduced IGF-I acts on the endocrine pancreas in the same way as administered IGF-I. Objective: To compare the effects of the two hormones on the endocrine pancreas of hypophysectomized rats. Methods: Animals were infused for 2 days, via miniosmotic pumps, with IGF-I (300mg/day), GH (200mU/day) or vehicle. We measured (i) glucose, IGF-I, insulin, C-peptide and glucagon in serum and (ii) IGF-I, insulin and glucagon mRNAs and peptides in the pancreas by radioimmunoassay, immunohistochemistry and northern analysis. Results: Both GH and IGF-I treatment increased serum and pancreatic IGF-I but, unlike GH, IGF-I treatment strongly reduced serum insulin and C-peptide (and, to a lesser extent, serum glucagon). Nevertheless, the animals did not become hyperglycaemic. GH, but not IGF-I, increased pancreatic insulin and glucagon content, as also indicated by immunohistochemistry, and increased IGF-I mRNA. Neither GH nor IGF-I caused significant changes in insulin and glucagon mRNA. Conclusions: The decrease in serum insulin and C-peptide by IGF-I treatment without significant changes in insulin gene expression and pancreatic insulin content suggests inhibition of insulin secretion. Within this setting, the absence of hyperglycaemia points to enhanced insulin sensitivity, although an insulin-like action of infused IGF-I may have partially compensated for the decreased insulin concentrations. GH-induced circulating or pancreatic IGF-I, or both, does not mimic the pancreatic effects of infused IGF-I in the absence of GH, suggesting that GH may counteract the action of GH-induced IGF-I on the endocrine pancreas. European Journal of Endocrinology 151 223‐231
- Published
- 2004
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