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Resumen: Introducción: La hormona de crecimiento (GH) y el factor de crecimiento similar a la insulina tipo 1 (IGF-1) tienen efecto modulador sobre la funcionalidad intestinal y la microbiota. Nuestro objetivo fue investigar si los pacientes con déficit de GH y, por lo tanto, con niveles bajos de GH e IGF-1 se asocian con cambios en la fisiología/integridad intestinal, así como en la composición de la microbiota intestinal. Material y métodos: Se realizó un estudio de casos y controles en 21 pacientes con déficit de GH previo al inicio y tras 6 meses de tratamiento con GH y en 20 controles sanos. Se estudiaron los cambios antropométricos, analíticos, de translocación bacteriana y también se determinó la composición del microbioma mediante secuenciación masiva del gen del ARNr 16S. Resultados: El déficit de GH se acompañó de un incremento significativo en los niveles séricos de sCD14, un marcador de translocación bacteriana (p

To determine the detection rate of IGF-1 variants in a clinical population and assess their implications. IGF-1 variants were detected based on their predicted mass-to-charge ratios. Most variants were distinguished by their isotopic distribution and relative retention times. A67T and A70T were distinguished with MS/MS. Patient specimens with a detected variant were de-identified for DNA sequencing to confirm the polymorphism. Of the 243,808 patients screened, 1,099 patients containing IGF-1 variants were identified (0.45 %, or 4,508 occurrences per million). Seven patients were identified as homozygous or double heterozygous. Majority of variants (98 %) had amino acid substitutions located at the C-terminus (A62T, P66A, A67S, A67V, A67T, A70T). Isobaric variants A38V and A67V were detected more frequently in children than in adults. Six previously unreported variants were identified: Y31H, S33P, T41I, R50Q, R56K, and A62T. Compared with the overall population, z-score distribution of patients with IGF-1 variants was shifted toward negative levels (median z-score −1.4); however, it resembled the overall population when corrected for heterozygosity. Chromatographic peak area of some variants differed from that of the WT IGF-1 present in the same patient. In the IGF-1 test reports by LC-MS, the concentrations only account for half the total IGF-1 for patients with heterozygous IGF-1 variants. An IGF-1 variant may change the binding to its receptor and/or its binding proteins, affecting its activity and half-life in circulation. Variants located in or close to the C-domain may be pathogenic. Cross-species sequence comparison indicates that A38V and A70T may have some degree of pathogenicity. [ABSTRACT FROM AUTHOR]

VEGFA, PlGF and IGF-1 are three main angiogenic factors which play significant roles in embryo implantation. However, the relationship between serum expressions of VEGFA, PlGF and IGF-1 and pregnancy outcomes has not been fully illustrated. In this study, serum specimens were collected precisely on day 7 after the LH surge in a natural non-conception cycle from 38 infertile patients who underwent frozen embryo transfer (FET) treatment. ELISA was used to determine the concentrations of VEGFA, PlGF and IGF-1. Serum levels of VEGFA, PlGF and IGF-1 were compared between patients who conceived (n=25) and who did not (n=13). Correlation and linear regression analyses were used to investigate the correlations of serum angiogenic factors and β-hCG MoM levels in the pregnant group. The results demonstrated that no significant difference was found in serum VEGFA, PlGF or IGF-1 concentration between pregnant and non-pregnant women. Spearman correlation analysis revealed a positive correlation between IGF-1 concentration and β-hCG level in pregnant participants (rs = 0.490, p = 0.013). In conclusion, serum IGF-1 level correlated positively with β-hCG level in pregnant women, which may provide information on the prognostic value of IGF-1 in this group of women. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) frequently exhibits hyperinsulinemia due to insulin resistance, but there are many unknown aspects of this disease. This report presents the case of a 31-year-old woman with PCOS and type B insulin resistance syndrome (TBIRS). The patient had repeated hyperglycemia and hypoglycemia, and prominent hyperinsulinemia. The insulin receptor antibody was positive, leading to a diagnosis of TBIRS. She also had amenorrhea during the previous 3 months, high blood testosterone levels, and enlarged polycystic ovaries, leading to a diagnosis of PCOS at the same time. The patient was treated with glucocorticoid for TBIRS. The insulin receptor antibody eliminated at 8 weeks after initiation of glucocorticoid treatment, and the blood glucose levels and hyperinsulinemia improved at 9 weeks. Then, the enlargement of both ovaries diminished at 32 weeks, and the menstruation had normalized since 36 weeks. The blood testosterone level normalized at 41 weeks. To the best of our knowledge, this is the first report to demonstrate that enlarged polycystic ovaries and a menstrual disorder in TBIRS improved after glucocorticoid treatment. It is possible that elimination of insulin receptor antibodies by glucocorticoid treatment attenuated insulin resistance and subsequently improved PCOS in TBIRS.

Through artificial selection and inbreeding, strains of laboratory mice have been developed that vary in the expression of a single or suite of desired traits valuable to biomedical research. In addition to the selected trait(s), these strains also display variation in pelage color, body size, physiology, and life history. This article exploits the broad phenotypic variation across lab mouse strains to evaluate the relationships between life history and metabolism. Life history variation tends to exist along a fast-slow continuum. There has been considerable interest in understanding the ecological and evolutionary factors underlying life history variation and the physiological and metabolic processes that support them. Yet it remains unclear how these key traits scale across hierarchical levels, as ambiguous empirical support has been garnered at the intraspecific level. Within-species investigations have been thwarted by methodological constraints and environmental factors that obscure the genetic architecture underlying the hypothesized functional integration of life history and metabolic traits. In this analysis, we used the publicly available Mouse Phenome Database by the Jackson Laboratory to investigate the relationships among life history traits (e.g., body size, reproduction, and life span) and metabolic traits (e.g., daily energy expenditure and insulin-like growth factor 1 concentration). Our findings revealed significant variation in reproductive characteristics across strains of mice as well as relationships among life history and metabolic traits. We found evidence of variation along the fast-slow life history continuum, though the direction of some relationships among these traits deviated from interspecific predictions laid out in previous literature. Furthermore, our results suggest that the strength of these relationships are strongest earlier in life. [ABSTRACT FROM AUTHOR]

We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single‐frequency, high‐power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low‐power‐density, single‐transducer, dual‐frequency US (ISPTA = 213 mW/cm2) and MBs of different sizes coated with insulin‐like growth factor 1 (IGF‐1). This study is the first to investigate the drug‐coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug‐coating efficiency was significantly higher for large‐sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual‐frequency US and large MB size delivered the most IGF‐1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF‐1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual‐frequency US and large MBs (D‐USMB) than in control animals treated with round window soaking (RWS). The IGF‐1 delivery efficiency was 10.15 times greater with the combination of single‐frequency US and large size MBs (S‐USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF‐1 in the basal turn in the D‐USMB and S‐USMB groups than in the RWS group. In the second and third turns, the D‐USMB group showed the greatest IGF‐1 distribution. Hearing assessments revealed no significant differences among the D‐USMB, S‐USMB, and RWS groups. In conclusion, the combination of single‐transducer dual‐frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF‐1, to the inner ear. [ABSTRACT FROM AUTHOR]

Understanding the relationship between growth and gonadal development is essential for breeding programs and studying teleost sexual development. This study investigated the growth and gonadal development of captive-reared false clown anemonefish (Amphiprion ocellaris) aged one to eight months. We performed histological analysis and quantified insulin-like growth factor-1 (igf1) mRNA transcripts. The fish exhibited a maximum specific growth rate of 0.56 ± 0.11% day-1 at two months, with a negative allometric length-weight relationship. Histological examination revealed ovarian differentiation commenced in the third month, while male germ cells progressed rapidly. Ovotestis formation occurred between the fourth and eighth month, with primary growth stage oocytes being predominant. Ovarian tissue consistently occupies a larger area than testicular tissue. Expression levels of igf1 in the liver peaked at eight months, with the highest expression observed in gonadal tissues at two months, which decreased significantly in older fish. These findings suggest a potential role igf1 in ovarian differentiation and the growth of primary oocytes. Further investigations are warranted to explore the interplay between igf1 expression and other regulatory factors. This research enhances our understanding of fish reproductive biology and has implications for the captive management of false clownfish. [ABSTRACT FROM AUTHOR]

Abstract We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single‐frequency, high‐power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low‐power‐density, single‐transducer, dual‐frequency US (ISPTA = 213 mW/cm2) and MBs of different sizes coated with insulin‐like growth factor 1 (IGF‐1). This study is the first to investigate the drug‐coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug‐coating efficiency was significantly higher for large‐sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual‐frequency US and large MB size delivered the most IGF‐1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF‐1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual‐frequency US and large MBs (D‐USMB) than in control animals treated with round window soaking (RWS). The IGF‐1 delivery efficiency was 10.15 times greater with the combination of single‐frequency US and large size MBs (S‐USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF‐1 in the basal turn in the D‐USMB and S‐USMB groups than in the RWS group. In the second and third turns, the D‐USMB group showed the greatest IGF‐1 distribution. Hearing assessments revealed no significant differences among the D‐USMB, S‐USMB, and RWS groups. In conclusion, the combination of single‐transducer dual‐frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF‐1, to the inner ear.

Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review article aims to provide a comprehensive view of the interplay between GH and IGF-1 and metabolism within the context of obesity. We conducted a systematic review of the literature that was published from 1993 to 2023, using MEDLINE, Embase, and Cochrane databases. We included studies that investigated the effects of GH and IGF-1 on adipose tissue metabolism, energy balance, and weight regulation in humans and animals. Our review highlights the physiological functions of GH and IGF-1 in adipose tissue metabolism, including lipolysis and adipogenesis. We also discuss the potential mechanisms underlying the effects of these hormones on energy balance, such as their influence on insulin sensitivity and appetite regulation. Additionally, we summarize the current evidence regarding the efficacy and safety of GH and IGF-1 as therapeutic targets for managing obesity, including in pharmacological interventions and hormone replacement therapy. Finally, we address the challenges and limitations of targeting GH and IGF-1 in obesity management. [ABSTRACT FROM AUTHOR]

Calibration is an important source of variability in liquid chromatography mass spectrometry (LC-MS) methods for insulin-like growth factor 1 (IGF-1). This study investigated the impact of different calibrator matrices on IGF-1 measurements by LC-MS. Moreover, the comparability of immunoassays and LC-MS was assessed. Calibrators from 12.5 to 2009 ng/ml were prepared by spiking WHO international Standard (ID 02/254 NIBSC, UK) into the following matrices: native human plasma, fresh charcoal-treated human plasma (FCTHP), old charcoal-treated human plasma, deionized water, bovine serum albumin (BSA), and rat plasma (RP). A validated in-house LC-MS method was calibrated repeatedly with these calibrators. Then, serum samples from 197 growth hormone excess and deficiency patients were analysed with each calibration. The seven calibration curves had different slopes leading to markedly different patient results. The largest differences in IGF-1 concentration from the median (interquartile range) was observed with the calibrator in water and the calibrator in RP (336.4 [279.6–417.0] vs. 112.5 [71.2–171.2], p < 0.001). The smallest difference was observed with calibrators in FCTHP and BSA (141.8 [102.0–198.5] vs. 127.9 [86.9–186.0], p < 0.049). Compared to LC-MS with calibrators in FCTHP, immunoassays showed relevant proportional bias (range: −43% to −68%), constant bias (range: 22.84 to 57.29 ng/ml) and pronounced scatter. Comparing the immunoassays with each other revealed proportional bias of up to 24%. The calibrator matrix is critical for the measurement of IGF-1 by LC-MS. Regardless of the calibrator matrix, LC-MS shows poor agreement with immunoassays. Also, the agreement between different immunoassays is variable. [ABSTRACT FROM AUTHOR]

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCUmediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth. [ABSTRACT FROM AUTHOR]

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.

PCOS or polycystic ovary syndrome is a common endocrine disorder that occurs during the reproductive age in females. It manifests in the form of a wide range of symptoms including (but not limited to) hirsutism, amenorrhea, oligomenorrhea, obesity, acne vulgaris, infertility, alopecia, and insulin resistance. The incidence of depression in PCOS population is increasing as compared to the general population. Increased depression in PCOS significantly alters the quality of life (QOL) of affected females. Also, self-esteem is found to be low in both depression and PCOS. The loss in self-esteem in such patients can be largely attributed to the associated factors including (but not limited to) obesity, acne, androgenic alopecia, and hirsutism. The reason behind the occurrence of depression in PCOS remains elusive to date. Literature suggests that there is an overlap of clinical symptoms between depression and PCOS. As the symptoms overlap, there is a possibility of common associations between depression, PCOS, and PCOS-associated abnormalities including insulin resistance (IR), obesity, CVD, and androgen excess. Studies demonstrate that depression is an inflammatory disorder marked with increased levels of inflammatory markers. On the other hand, PCOS is also regarded as a pro-inflammatory state that is characterized by increased levels of pro-inflammatory markers. Thus, there is a possibility of an inflammatory relationship existing between depression and PCOS. It is also possible that the inflammatory markers in PCOS can cross the blood–brain barrier (BBB) leading to the development of depression. Through the present review, we have attempted to shed light on common associations/shared links between depression and PCOS with respect to the levels of cortisol, androgen, vitamin D, neurotransmitters, monoaminoxidase (MAO), and insulin-like growth factor-1 (IGF-1). Tracking down common associations between depression and PCOS will help find potential drug therapies and improve the QOL of females with depression in PCOS. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence shows that physical exercise has a positive effect on the release of neurotrophic factors and myokines. However, evidence regarding the optimal type of physical exercise for these release is still lacking. The aim of this study was to assess the acute and chronic effects of open-skill exercise (OSE) compared to closed-skill exercise (CSE) on serum and plasma levels of brain derived neurotrophic factor (BDNFS, BDNFP), and serum levels of insulin like growth factor 1 (IGF-1), and interleukin 6 (IL-6) in healthy older adults. Methods To investigate acute effects, thirty-eight participants were randomly assigned to either an intervention (badminton (aOSE) and bicycling (aCSE), n = 24, 65.83 ± 5.98 years) or control group (reading (CG), n = 14, 67.07 ± 2.37 years). Blood samples were taken immediately before and 5 min after each condition. During each condition, heart rate was monitored. The mean heart rate of aOSE and aCSE were equivalent (65 ± 5% of heart rate reserve). In a subsequent 12-week training-intervention, twenty-two participants were randomly assigned to either a sport-games (cOSE, n = 6, 64.50 ± 6.32) or a strength-endurance training (cCSE, n = 9, 64.89 ± 3.51) group to assess for chronic effects. Training intensity for both groups was adjusted to a subjective perceived exertion using the CR-10 scale (value 7). Blood samples were taken within one day after the training-intervention. Results BDNFS, BDNFP, IGF-1, and IL-6 levels increased after a single exercise session of 30 min. After 12 weeks of training BDNFS and IL-6 levels were elevated, whereas IGF-1 levels were reduced in both groups. However, only in the cOSE group these changes were significant. We could not find any significant differences between the exercise types. Conclusion Our results indicate that both exercise types are efficient to acutely increase BDNFS, BDNFP, IGF-1 and IL-6 serum levels in healthy older adults. Additionally, our results tend to support that OSE is more effective for improving basal BDNFS levels after 12 weeks of training.

Background: Prevention of hearing loss via addressing potentially modifiable risk factors may offer means of reducing the global burden of hearing loss. Prior studies reported associations between individual markers of inflammation and risk of hearing impairment. Allostatic load is an index of cumulative physiological stressors, including inflammation, to multiple biological systems. Our aims were to investigate associations between allostatic load and both audiometric and self-reported hearing impairment and examine whether associations are stronger over time due to prolonged high allostatic load. Methods: Data were taken from the English Longitudinal Study of Ageing (ELSA), a nationally representative study of people aged 50+ living in England over 3 time points between 2008 and 2014. Allostatic load score was comprised of thirteen different measures available at baseline and 4 years post-baseline (high-density lipoprotein/total cholesterol, triglyceride, fibrinogen, haemoglobin A1c, C-reactive protein, insulin-like growth factor 1 (IGF-1), systolic and diastolic blood pressure, mean arterial pressure, resting pulse rate, peak expiratory flow, BMI and waist circumference), measured using clinical cut-off points for normal biomarker parameters. Hearing acuity was measured with a simple handheld tone-producing device at follow-up 7 years post-baseline, while self-reported hearing impairment was measured at time point. Results: We included samples of 4373 and 4430 for the cross-sectional and longitudinal analysis, respectively. In the cross-sectional model high allostatic load was associated both self-reported (OR = 1.08, 95% CI 1.0,1.1; p

Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review article aims to provide a comprehensive view of the interplay between GH and IGF-1 and metabolism within the context of obesity. We conducted a systematic review of the literature that was published from 1993 to 2023, using MEDLINE, Embase, and Cochrane databases. We included studies that investigated the effects of GH and IGF-1 on adipose tissue metabolism, energy balance, and weight regulation in humans and animals. Our review highlights the physiological functions of GH and IGF-1 in adipose tissue metabolism, including lipolysis and adipogenesis. We also discuss the potential mechanisms underlying the effects of these hormones on energy balance, such as their influence on insulin sensitivity and appetite regulation. Additionally, we summarize the current evidence regarding the efficacy and safety of GH and IGF-1 as therapeutic targets for managing obesity, including in pharmacological interventions and hormone replacement therapy. Finally, we address the challenges and limitations of targeting GH and IGF-1 in obesity management.

Objective: Adults with cerebral palsy (CP) often have impaired cognitive functions. CP also has deteriorations in multiple quality-of-life (QoL) domains. The bio-psycho-social health psychology model posits that biological factor interacts with social and psychological functions. However, the biological determinant of psycho-social and functional outcomes in CP has been scarcely examined. Circulating Insulin-like growth factor-1 (IGF-1) is associated with cognitive deficits in older adults, we thus aimed to examine the associations of circulating IGF-1 with: (1) objectively measured cognitive functions, (2) self-reported cognitive functions, and (3) QoL measures in adults diagnosed with CP. Methods: Seventy-two adults with CP and varying degrees of cognitive functions were recruited from an accredited clinical motion analysis laboratory at a regional Children's Hospital. Circulating IGF-1 was measured using post-fasting serum. The Wechsler Adult Intelligence Scale (WAIS) tests were administered to assess multiple cognitive functions, whereas the Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure multiple domains of self-reported health, including cognitive complaints and eight QoL domains. Results: Sixty-eight participants had complete data [mean age = 25 (SD = 5.3), female = 52.8%]. Controlling for covariates, circulating IGF-1 was associated with multiple cognitive domains, including positively with declarative memory and executive function and inversely with visual-spatial and motor skills, and processing speed, while no association with subjective memory complaint was detected. Circulating IGF-1 was also inversely associated with four QoL domains, including depressive symptoms, executive function, physical function, and social roles and activities. Conclusions: In CP, circulating IGF-1 might be a useful biological determinant of objective cognitive functions and several quality-of-life domains commonly impaired in CP. [ABSTRACT FROM AUTHOR]

ObjectiveAdults with cerebral palsy (CP) often have impaired cognitive functions. CP also has deteriorations in multiple quality-of-life (QoL) domains. The bio-psycho-social health psychology model posits that biological factor interacts with social and psychological functions. However, the biological determinant of psycho-social and functional outcomes in CP has been scarcely examined. Circulating Insulin-like growth factor-1 (IGF-1) is associated with cognitive deficits in older adults, we thus aimed to examine the associations of circulating IGF-1 with: (1) objectively measured cognitive functions, (2) self-reported cognitive functions, and (3) QoL measures in adults diagnosed with CP.MethodsSeventy-two adults with CP and varying degrees of cognitive functions were recruited from an accredited clinical motion analysis laboratory at a regional Children's Hospital. Circulating IGF-1 was measured using post-fasting serum. The Wechsler Adult Intelligence Scale (WAIS) tests were administered to assess multiple cognitive functions, whereas the Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure multiple domains of self-reported health, including cognitive complaints and eight QoL domains.ResultsSixty-eight participants had complete data [mean age = 25 (SD = 5.3), female = 52.8%]. Controlling for covariates, circulating IGF-1 was associated with multiple cognitive domains, including positively with declarative memory and executive function and inversely with visual-spatial and motor skills, and processing speed, while no association with subjective memory complaint was detected. Circulating IGF-1 was also inversely associated with four QoL domains, including depressive symptoms, executive function, physical function, and social roles and activities.ConclusionsIn CP, circulating IGF-1 might be a useful biological determinant of objective cognitive functions and several quality-of-life domains commonly impaired in CP.

Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found. • Acromegaly/hypersomatotropism is 10x more common in cats than humans. • Somatotroph tumours are the main cause of acromegaly in humans and cats. • Acromegalic humans and cats share common clinical features. • Diagnosis of acromegaly mainly relies on serum IGF-1 in humans and cats. • Treatment consists of surgery, drugs or radiation, not always available in vet medicine. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence shows that physical exercise has a positive effect on the release of neurotrophic factors and myokines. However, evidence regarding the optimal type of physical exercise for these release is still lacking. The aim of this study was to assess the acute and chronic effects of open-skill exercise (OSE) compared to closed-skill exercise (CSE) on serum and plasma levels of brain derived neurotrophic factor (BDNFS, BDNFP), and serum levels of insulin like growth factor 1 (IGF-1), and interleukin 6 (IL-6) in healthy older adults.Methods: To investigate acute effects, thirty-eight participants were randomly assigned to either an intervention (badminton (aOSE) and bicycling (aCSE), n  = 24, 65.83 ± 5.98 years) or control group (reading (CG), n  = 14, 67.07 ± 2.37 years). Blood samples were taken immediately before and 5 min after each condition. During each condition, heart rate was monitored. The mean heart rate of aOSE and aCSE were equivalent (65 ± 5% of heart rate reserve). In a subsequent 12-week training-intervention, twenty-two participants were randomly assigned to either a sport-games (cOSE, n  = 6, 64.50 ± 6.32) or a strength-endurance training (cCSE, n  = 9, 64.89 ± 3.51) group to assess for chronic effects. Training intensity for both groups was adjusted to a subjective perceived exertion using the CR-10 scale (value 7). Blood samples were taken within one day after the training-intervention.Results: BDNFS, BDNFP, IGF-1, and IL-6 levels increased after a single exercise session of 30 min. After 12 weeks of training BDNFS and IL-6 levels were elevated, whereas IGF-1 levels were reduced in both groups. However, only in the cOSE group these changes were significant. We could not find any significant differences between the exercise types.Conclusion: Our results indicate that both exercise types are efficient to acutely increase BDNFS, BDNFP, IGF-1 and IL-6 serum levels in healthy older adults. Additionally, our results tend to support that OSE is more effective for improving basal BDNFS levels after 12 weeks of training. [ABSTRACT FROM AUTHOR]

Abstract Background Research evidence accumulated in the past years in both rodent and human models for autism spectrum disorders (ASD) have established insulin-like growth factor 1 (IGF-1) as one of the most promising ASD therapeutic interventions to date. ASD is phenotypically and etiologically heterogeneous, making it challenging to uncover the underlying genetic and cellular pathophysiology of the condition; and to efficiently design drugs with widespread clinical benefits. While IGF-1 effects have been comprehensively studied in the literature, how IGF-1 activity may lead to therapeutic recovery in the ASD context is still largely unknown. Methods In this study, we used a previously characterized neuronal population derived from induced pluripotent stem cells (iPSC) from neurotypical controls and idiopathic ASD individuals to study the transcriptional signature of acutely and chronically IGF-1-treated cells. Results We present a comprehensive list of differentially regulated genes and molecular interactions resulting from IGF-1 exposure in developing neurons from controls and ASD individuals. Our results indicate that IGF-1 treatment has a different impact on neurons from ASD patients compared to controls. Response to IGF-1 treatment in neurons derived from ASD patients was heterogeneous and correlated with IGF-1 receptor expression, indicating that IGF-1 response may have responder and non-responder distinctions across cohorts of ASD patients. Our results suggest that caution should be used when predicting the effect of IGF-1 treatment on ASD patients using neurotypical controls. Instead, IGF-1 response should be studied in the context of ASD patients’ neural cells. Limitations The limitation of our study is that our cohort of eight sporadic ASD individuals is comorbid with macrocephaly in childhood. Future studies will address weather downstream transcriptional response of IGF-1 is comparable in non-macrocephalic ASD cohorts. Conclusions The results presented in this study provide an important resource for researchers in the ASD field and underscore the necessity of using ASD patient lines to explore ASD neuronal-specific responses to drugs such as IGF-1. This study further helps to identify candidate pathways and targets for effective clinical intervention and may help to inform clinical trials in the future.

Introduction: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have modulatory effects on bowel function and its microbiota. Our aim was to investigate whether low levels of GH and IGF-1 in patients with GH deficiency are associated with changes in gut physiology/integrity as well as in the composition of the gut microbiota., Materials and Methods: We conducted a case-control study in 21 patients with GH deficiency, at baseline and after 6 months of GH treatment, and in 20 healthy controls. We analysed changes in anthropometric and laboratory characteristics and bacterial translocation and studied the composition of the microbiome by means of massive 16S rRNA gene sequencing., Results: Growth hormone deficiency was accompanied by a significant increase in serum levels of sCD14, a marker of bacterial translocation (P < .01). This increase was reversed by GH treatment. We did not find any differences in the composition or α- or β-diversity of the gut microbiota after treatment or between cases and controls., Conclusions: Our work is the first to demonstrate that the presence of GH deficiency is not associated with differences in gut microbiota composition in comparison with healthy controls, and changes in microbiota composition are also not found after 6 months of treatment. However, GH deficiency and low IGF-1 levels were associated with an increase in bacterial translocation, which had reversed after treatment., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background Serum insulin-like growth factor 1 (sIGF-1) is an important growth factor in childhood. However, studies on sIGF-1 among children from low-income countries are few, and the role of body composition is unknown. Objectives To assess the associations of anthropometry, body composition, inflammation, and breastfeeding with sIGF-1 among children with moderate acute malnutrition (MAM). Methods A cross-sectional study based on admission data from 6- to 23-mo-old children with MAM participating in a nutrition intervention trial (Treatfood) in Burkina Faso. Linear regression analysis was used to identify correlates of sIGF-1. Results Among 1546 children, the median (IQR) sIGF-1 was 12 (8.2–18.3) ng/mL. sIGF-1 was highest at 6 mo, with a nadir ∼10–11 mo, and higher in girls than boys. Length-for-age z score (LAZ), weight-for-length z score (WLZ), and midupper arm circumference were positively associated with sIGF-1 (P  ≤ 0.001). Fat-free mass (FFM) was also positively associated, as sIGF-1 increased 1.5 (95% CI: 0.5, 2.5) ng/mL for each 1-kg increase in FFM. However, the association disappeared after adjustment for height. Elevated serum C-reactive protein and α1-acid glycoprotein were negatively associated with sIGF-1 (P  ≤ 0.001), as was fever (P  < 0.001) but not a positive malaria test per se (P  = 0.15). Children never breastfed had lower sIGF-1 (–5.1; 95% CI: –9.8, –0.3). Conclusions LAZ and WLZ were positively and inflammation negatively associated with sIGF-1. As all children were moderately malnourished and many had inflammation, this probably explains the very low median sIGF-1. The association of FFM with sIGF-1 was fully explained by height. There was a marked age pattern, with a nadir in late infancy, confirming findings from smaller studies from well-nourished populations. There is a need for prospective studies to disentangle the role of sIGF-1 in growth and health. This trial was registered at https://www.isrctn.com as ISRCTN42569496. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the composition including concentrations of IGF-1, IgG and Vit A in colostrum and their effects by litter size and goat parity in 3 groups of goats; Black Bengal (BB), Saanen (SA) and their crossbred (BBSA). Thirty-eight goats were used (23 BB, 7 BBSA and 8 SA). The composition (fat, protein, lactose and total solid; TS) in colostrum (Day 0; D0) and milk (Day 4; D4 and Day 7; D7) were measured. The IGF-1, IgG concentrations were analysed in some samples collected at D0, D4 and D7 while Vit A was analysed only in colostrum. The results showed that colostrum components were similar among experimental groups. However, the colostral IGF-1 concentration of BBSA (983.0 ± 163.6 ng/mL) was higher than that of BB (340.7 ± 85.5 ng/mL, p < 0.01) and SA (417.1 ± 93.9 ng/mL, p < 0.01). The colostral IgG concentration of BB (8.2 ± 0.9 mg/mL) was lower than that of BBSA (12.9 ± 1.7 mg/mL, p < 0.05) and SA (12.9 ± 1.0 mg/mL, p < 0.01). Colostral Vit A concentration in BBSA (787.2 ± 152.6 µg/100 gm) was higher than that in BB (388.9 ± 84.3 µg/100 gm, p < 0.05) but was not different from SA (522.8 ± 96.9 µg/100 gm). Colostrum from all groups contained higher protein and TS but was lower in lactose concentration than milk. The IGF-1 and IgG concentrations in colostrum were much higher than in milk both D4 and D7 (p < 0.001). Additionally, litter size had no effects on colostrum contents but colostrum from goats with a higher parity number had higher IgG concentration. It is concluded that colostrum from BBSA may be superior when fed to BB newborn goats in terms of higher IGF-1, IgG and Vit A contents. Moreover, colostrum from goats with a high parity number contained more IgG content. [ABSTRACT FROM AUTHOR]

Objectives The loss of muscle mass in older adults is attributed to the impaired ability of the skeletal muscle in response to anabolic stimuli and the increased activation of the proteolytic signaling pathway. With increasing age, plasma concentrations of circulating anabolic hormones and growth factors, e.g. testosterone, Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) are also diminished. Resistance Training (RT) promotes positive adaptations that attenuate the harmful effects of aging. The aim of this investigation was evaluation the impact of RT with Low Load (LL) and high load (HL) on the testosterone, IGF-1, IGFBP-3 levels and functional adaptations in older women. Methods & Materials A total of 28 older women (Mean±SD age: 63.14±2.51 y) eligible to participate in this study were randomly assigned into three groups of RT with Low Load (RT-LL) (30٪ 1RM [one repetition maximum test]), RT group with High Load (RT-HL) (80٪ 1RM) and control group. Both training groups performed the exercise until fatigue. The minimum number of repetitions for the RT-LL group was 20 and for the RT-HL group 8. The RT program was executed three sessions per week for 8 weeks. Testosterone, IGF-1, IGFBP-3, lower body muscular strength, and muscular endurance of the subjects were measured before and after the intervention. Results No significant changes were observed in testosterone, IGF-1, and IGFBP-3 levels after 8 weeks of RT (P>0.05). Both training groups significantly increased the lower body muscular strength and muscular endurance (P0.05). Conclusion Based on the study findings, RT-LL until the fatigue may affect performance adaptations resulting from exercise and provide an appropriate alternative to RT-HL in older people.

Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) are important biomarkers in research and diagnosis of growth disorders. Quantitative analysis is performed using various ligand-binding assays or enzymatic digestion LC-MS/MS methods, whose widespread adoption is hampered by time-consuming sample preparation procedures. We present a simple and fast antibody-free LC-MS/MS method for the quantification of intact IGF-1 and IGF-2 in human plasma. The method requires 50 μL of plasma and uses fully 15N-labelled IGF-1 as internal standard. It features trifluoroethanol (TFE)-based IGF/IGF-binding protein complex dissociation and a two-step selective protein precipitation workflow, using 5% acetic acid in 80/20 acetone/acetonitrile (precipitation 1) and ice-cold ethanol (precipitation 2). Detection of intact IGF-1 and IGF-2 is performed by means of a Waters XEVO TQ-S triple quadrupole mass spectrometer in positive electrospray ionisation (ESI+) mode. Lower limits of quantification were 5.9 ng/mL for IGF-1 and 8.4 ng/mL for IGF-2. Intra-assay imprecision was below 4.5% and inter-assay imprecision was below 5.8% for both analytes. An excellent correlation was found between nominal and measured concentrations of the WHO reference standard for IGF-1. Comparison with the IDS-iSYS IGF-1 immunoassay showed good correlation (R2 > 0.97), although a significant bias was observed with the immunoassay giving substantially higher concentrations. The LC-MS/MS method described here allows for reliable and simultaneous quantification of IGF-1 and IGF-2 in plasma, without the need for enzymatic digestion. The method can be readily implemented in clinical mass spectrometry laboratories and has the potential to be adapted for the analysis of different similarly sized peptide hormones. [ABSTRACT FROM AUTHOR]

Background: Unstable angina pectoris (UAP) is a type of Coronary artery disease (CAD) characterized by a series of angina symptoms. Insulin-like growth factor 1 (IGF-1) system may be related to CAD. However, the correlation between the IGF-1 system, metabolism, and gut microbiota has not been studied. In the present study, we investigated the alterations of serum IGF-1 system, metabolomics, and gut microbiota in patients with UAP. Methods: Serum and stool samples from healthy volunteers and UAP patients were collected. Serum metabolomics, PAPP-A, IGF-1, IGFBP-4, STC2, hs-CRP, TNF-α, and IL-6 were detected in serum samples by LC-MS, and commercial ELISA kits, respectively. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography. 16S rDNA was used to measure the changes of the gut microbiota. The correlation of the above indicators was analyzed. Results: There were 24 upregulated and 31 downregulated metabolites in the serum of UAP patients compared to those in the controls. Pathway analysis showed that these metabolites were enriched in pathways including linoleic acid metabolism, amino acid metabolism, starch metabolism, sucrose metabolism, and citrate cycle (TCA cycle), etc. Additionally, the UAP patients had lower fecal levels of 2-hydroxyisobutyric acid and succinic acid. 16S rDNA sequencing results showed that the relative abundances of Bacteroidetes, Synergistetes, Lactobacillaceae, Burkholderiaceae, Synergistaceae, and Subdoligranulum were significantly higher in the UAP patients than the healthy subjects. Moreover, the UAP patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokines (hs-CRP, TNF-α, and IL-6) levels than the healthy controls. Furthermore, there was a strong correlation between serum amino acids and IL-6, which played an important role in the development of UAP. Conclusions: These results indicated that the UAP patients had decreased serum IGF-1 level and imbalanced amino acids metabolism, which may be caused by the altered gut microbiota. It may provide a new therapeutic strategy for unstable angina pectoris.

Purpose To investigate the association between insulin-like growth factor 1 (IGF1) single-nucleotide polymorphisms (SNPs) and myopia in a young Chinese population. Methods A total of 654 Chinese children aged 6–13 years from one primary school participated in our study and underwent a series of comprehensive ocular examinations, including cycloplegic refraction and measurements of axial length. Myopia was defined as a spherical equivalence (SE) ≤ −0.5 D in the worse eye. In total, six tagging SNPs of IGF1 were genotyped using the PCR-LDR (Polymerase Chain Reaction-Ligation Detection Reaction) method. We tested four different genetic modes (the allele, dominant, recessive, and additive models) of these SNPs and used multivariate logistic regression to calculate the effect of SNPs on myopia. In addition, we conducted a haplotype analysis with a variable-sized slide-window strategy. Results Overall, 281 myopic children and 373 non-myopic controls were included in the analysis. The SNP rs2162679 showed a statistical difference between the two groups in both the allele (p = 0.0474) and additive (p = 0.0497) models. After adjusting for age and gender, children with the genotype AA in the SNP rs2162679 had a higher risk of myopia than those with the genotype GG (OR = 2.219, 95% CI [1.218–4.039], p = 0.009). All haplotypes that varied significantly between the two groups contained the SNP rs2162679, and the four-SNP window rs5742653–rs2162679 had the lowest p value (Chi square = 5.768, p = 0.0163). However, after permutation tests, none of the associations remained statistically significant. Conclusion The SNP rs2162679 in IGF1 was associated with myopia in a young Chinese population. The G allele in the SNP rs2162679 may protect against myopia.

Background: Research evidence accumulated in the past years in both rodent and human models for autism spectrum disorders (ASD) have established insulin-like growth factor 1 (IGF-1) as one of the most promising ASD therapeutic interventions to date. ASD is phenotypically and etiologically heterogeneous, making it challenging to uncover the underlying genetic and cellular pathophysiology of the condition; and to efficiently design drugs with widespread clinical benefits. While IGF-1 effects have been comprehensively studied in the literature, how IGF-1 activity may lead to therapeutic recovery in the ASD context is still largely unknown. Methods: In this study, we used a previously characterized neuronal population derived from induced pluripotent stem cells (iPSC) from neurotypical controls and idiopathic ASD individuals to study the transcriptional signature of acutely and chronically IGF-1-treated cells. Results: We present a comprehensive list of differentially regulated genes and molecular interactions resulting from IGF-1 exposure in developing neurons from controls and ASD individuals. Our results indicate that IGF-1 treatment has a different impact on neurons from ASD patients compared to controls. Response to IGF-1 treatment in neurons derived from ASD patients was heterogeneous and correlated with IGF-1 receptor expression, indicating that IGF-1 response may have responder and non-responder distinctions across cohorts of ASD patients. Our results suggest that caution should be used when predicting the effect of IGF-1 treatment on ASD patients using neurotypical controls. Instead, IGF-1 response should be studied in the context of ASD patients' neural cells. Limitations: The limitation of our study is that our cohort of eight sporadic ASD individuals is comorbid with macrocephaly in childhood. Future studies will address weather downstream transcriptional response of IGF-1 is comparable in non-macrocephalic ASD cohorts. Conclusions: The results presented in this study provide an important resource for researchers in the ASD field and underscore the necessity of using ASD patient lines to explore ASD neuronal-specific responses to drugs such as IGF-1. This study further helps to identify candidate pathways and targets for effective clinical intervention and may help to inform clinical trials in the future. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

The present study aims to investigate the composition including concentrations of IGF-1, IgG and Vit A in colostrum and their effects by litter size and goat parity in 3 groups of goats; Black Bengal (BB), Saanen (SA) and their crossbred (BBSA). Thirty-eight goats were used (23 BB, 7 BBSA and 8 SA). The composition (fat, protein, lactose and total solid; TS) in colostrum (Day 0; D0) and milk (Day 4; D4 and Day 7; D7) were measured. The IGF-1, IgG concentrations were analysed in some samples collected at D0, D4 and D7 while Vit A was analysed only in colostrum. The results showed that colostrum components were similar among experimental groups. However, the colostral IGF-1 concentration of BBSA (983.0 ± 163.6 ng/mL) was higher than that of BB (340.7 ± 85.5 ng/mL, p < 0.01) and SA (417.1 ± 93.9 ng/mL, p < 0.01). The colostral IgG concentration of BB (8.2 ± 0.9 mg/mL) was lower than that of BBSA (12.9 ± 1.7 mg/mL, p < 0.05) and SA (12.9 ± 1.0 mg/mL, p < 0.01). Colostral Vit A concentration in BBSA (787.2 ± 152.6 µg/100 gm) was higher than that in BB (388.9 ± 84.3 µg/100 gm, p < 0.05) but was not different from SA (522.8 ± 96.9 µg/100 gm). Colostrum from all groups contained higher protein and TS but was lower in lactose concentration than milk. The IGF-1 and IgG concentrations in colostrum were much higher than in milk both D4 and D7 (p < 0.001). Additionally, litter size had no effects on colostrum contents but colostrum from goats with a higher parity number had higher IgG concentration. It is concluded that colostrum from BBSA may be superior when fed to BB newborn goats in terms of higher IGF-1, IgG and Vit A contents. Moreover, colostrum from goats with a high parity number contained more IgG content.

Recent studies have demonstrated that IGF-1 modulates the pluripotent differentiation of dental pulp stem cells (DPSCs). Although mTOR pathway activation has been showed as responsible for IGF-1 induced pluripotent differentiation, the mechanism that the IGF-1–mTOR pathway induces the neural differentiation of DPSCs is still unclear. In our research, we have demonstrated that 0–10 ng/mL IGF-1 had no obvious effect on the proliferation of DPSCs, but IGF-1 nonetheless enhances the neural differentiation of DPSCs in a dose-dependent manner. Simultaneously, we found that phosphorylated mTOR was up-regulated, which indicated the involvement of mTOR in the process. Rapamycin, an inhibitor of mTOR activity, can reverse the effect of DPSCs stimulated by IGF-1. Next, we studied the role of mTORC1 and mTORC2, two known mTOR complexes, in the neural differentiation of DPSCs. We found that inhibition of mTORC1 can severely restricts the neural differentiation of DPSCs. However, inhibition of mTORC2 has the opposite effect. This latter effect disappears when both rictor and mTOR are inhibited, showing that the mTORC2 effect is mTORC1 dependent. This study has expanded the role of mTOR in DPSCs neural differentiation regulated by IGF-1. [ABSTRACT FROM AUTHOR]

Abstract Polycystic ovary syndrome (PCOS) is an endocrine and metabolic heterogeneous disorder. The incidence of which reaches 5% to 10% among reproductive-age women. Abnormal folliculogenesis is considered to be a common characteristic of PCOS, but the cause of this disorder and its pathogenesis still remain uncertain. Previous studies had proved that dysregulation of microRNAs is related to the pathogenesis of PCOS. In this study, we investigated the effect of miR-323-3p on the human cumulus cells (CCs). We also investigated the underlying mechanisms of miR-323-3p on human granulosa-like tumor cell line (KGN) or primary human CCs by stimulating with Dihydrotestosterone (DHT). Our findings suggested that the level of miR-323-3p in human CCs of women with PCOS was down-regulated, compared with that of the control group. Moreover, the inhibition of the level of miR-323-3p could up-regulate of the steroidogenesis and promote the apoptosis in KGN cells. In addition, our data confirmed that the Insulin-like growth factor 1 (IGF-1) gene was the direct target of miR-323-3p. Furthermore, the mimic of miR-323-3p inhibited the expression of IGF-1, which down-regulated the levels of AR, AMHR-II, CYP19A, EGFR, and GATA-4. In conclusion, miR-323-3p targeting IGF-1 regulates the steroidogenesis and the activity of CCs, which plays an important role in the occurrence and development of PCOS. Our results have shown that miR-323-3p is a novel and promising molecular target for the improvement of the dysfunction of CCs in PCOS. Highlights • miR-323-3p expression in human cumulus cells and KGN cells • Effect of miR-323-3p on function of steroidogenesis synthesis and in KGN cells • Effect of miR-323-3p on cell viability and cell cycle in KGN cells • IGF-1 is a direct target of miR-323-3p. • Effect of IGF-1 on function of steroidogenesis synthesis in KGN cells [ABSTRACT FROM AUTHOR]

Background/Aims: The pathogenesis of Lumbar disc degeneration (LDD) has been extensively studied in the past. In particular, a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has been recently reported. However, an involvement of Insulin-like growth factor 1 (IGF-I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling pathway-mediated control of MMP3 in LDD has not been acknowledged. Methods: We examined the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) in resected discs in patients with LDD, compared to the fractured discs from traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and analyzed its effect on the activation of IGF-1R, Akt and MMP3. Results: LDD patients had significantly lower levels of serum IGF-1, and LDD discs had significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells, resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells. Conclusion: Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the development of LDD.

Polycystic ovary syndrome (PCOS) frequently exhibits hyperinsulinemia due to insulin resistance, but there are many unknown aspects of this disease. This report presents the case of a 31-year-old woman with PCOS and type B insulin resistance syndrome (TBIRS). The patient had repeated hyperglycemia and hypoglycemia, and prominent hyperinsulinemia. The insulin receptor antibody was positive, leading to a diagnosis of TBIRS. She also had amenorrhea during the previous 3 months, high blood testosterone levels, and enlarged polycystic ovaries, leading to a diagnosis of PCOS at the same time. The patient was treated with glucocorticoid for TBIRS. The insulin receptor antibody eliminated at 8 weeks after initiation of glucocorticoid treatment, and the blood glucose levels and hyperinsulinemia improved at 9 weeks. Then, the enlargement of both ovaries diminished at 32 weeks, and the menstruation had normalized since 36 weeks. The blood testosterone level normalized at 41 weeks. To the best of our knowledge, this is the first report to demonstrate that enlarged polycystic ovaries and a menstrual disorder in TBIRS improved after glucocorticoid treatment. It is possible that elimination of insulin receptor antibodies by glucocorticoid treatment attenuated insulin resistance and subsequently improved PCOS in TBIRS.

Objectives: To determine the detection rate of IGF-1 variants in a clinical population and assess their implications., Methods: IGF-1 variants were detected based on their predicted mass-to-charge ratios. Most variants were distinguished by their isotopic distribution and relative retention times. A67T and A70T were distinguished with MS/MS. Patient specimens with a detected variant were de-identified for DNA sequencing to confirm the polymorphism., Results: Of the 243,808 patients screened, 1,099 patients containing IGF-1 variants were identified (0.45 %, or 4,508 occurrences per million). Seven patients were identified as homozygous or double heterozygous. Majority of variants (98 %) had amino acid substitutions located at the C-terminus (A62T, P66A, A67S, A67V, A67T, A70T). Isobaric variants A38V and A67V were detected more frequently in children than in adults. Six previously unreported variants were identified: Y31H, S33P, T41I, R50Q, R56K, and A62T. Compared with the overall population, z-score distribution of patients with IGF-1 variants was shifted toward negative levels (median z-score -1.4); however, it resembled the overall population when corrected for heterozygosity. Chromatographic peak area of some variants differed from that of the WT IGF-1 present in the same patient., Conclusions: In the IGF-1 test reports by LC-MS, the concentrations only account for half the total IGF-1 for patients with heterozygous IGF-1 variants. An IGF-1 variant may change the binding to its receptor and/or its binding proteins, affecting its activity and half-life in circulation. Variants located in or close to the C-domain may be pathogenic. Cross-species sequence comparison indicates that A38V and A70T may have some degree of pathogenicity., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Abstract: Daily injections of growth hormone (GH) as replacement therapy in GH‐deficient (GHD) patients may cause poor compliance and inconvenience. C‐terminal peptide–modified human GH (MOD­4023) has been developed for once­weekly administration in GHD adults and children. In the present study, the pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous dose of MOD­4023 were evaluated in healthy Caucasian and Japanese adults, using a phase 1 double‐blind, vehicle‐controlled, randomized study design. The study was conducted in 42 healthy Japanese (n = 21) and Caucasian (n = 21) men receiving either MOD‐4023 at a dose of 2.5, 7.5, or 15 mg or vehicle. In the 2.5‐ and 7.5‐mg cohorts, no differences in mean MOD‐4023 serum concentration were found between Japanese and Caucasian subjects. A comparison of PK parameters in the 15‐mg group suggests a slower absorption rate of MOD‐4023 in Japanese subjects. PD analysis showed no apparent differences in IGF‐1 and IGFBP‐3 plasma concentrations between the Japanese and Caucasian subjects and indicated that a dose of 15 mg achieved the maximal effect in both ethnic groups. MOD‐4023 demonstrated a favorable safety profile and local tolerance following single‐dose subcutaneous administration. This study provides additional support for the development of MOD‐4023 as a long‐acting human growth hormone formulation for once‐weekly administration. [ABSTRACT FROM AUTHOR]

A study was carried out to assess the regulation of compensatory growth under different restriction feeding regimes in Labeo rohita juveniles by the interaction of various feed intake and growth regulating genes. A 60 day feeding trial was conducted with five treatment groups, Control (3% body weight, bw), T1 (alternate days), T2 (0.5% bw), T3 (1% bw) and T4 (2% bw) and feeding was done for first 30 days of the trial. For next 30 days, all the treatment groups were fed at a rate of 3% bw as in the control group. There was significant (p < 0.05) difference in the weight gain among the treatment groups with lowest FCR and highest PER was found in T2 group. Ghrelin gene mRNA levels were upregulated during first 30th days of the trial with highest expression levels in the T2 group. The expression levels of leptin gene mRNA were found significantly different (p < 0.05) among the treatments, which was down-regulated during initial 30 days and upregulated as the experiment progress towards 60th day. The IGF-1 mRNA expression levels were upregulated more in liver compared to the muscle tissue. The results of the study suggest that increased ghrelin levels and decreased leptin levels lead to hyperphagia during the onset of refeeding, which further triggers the compensatory growth in L. rohit a. The present study describes the molecular mechanism behind the compensatory growth following a different feed restriction regime in L. rohita which is regulated due to the interaction of different energy homeostasis and growth regulating genes. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of different dietary energy levels on serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as gene expression of their associated binding proteins and receptors in yak. Fifteen adult male yaks with BW of 276.1 ± 3.5 kg were allotted in three dietary groups and were fed with low (LE), medium (ME), and high energy (HE) level diet having different NEg of 5.5 MJ/kg, 6.2 MJ/kg, 6.9 MJ/kg, respectively. The effects of these treatments on ADG, BW, ADFI, and feed conversion ratio were significant (p < 0.05) throughout the experimental period. Serum GH concentration decreased (p < 0.05) with an increase in dietary energy level on d 30 and d 60. While IGF-1 concentration was higher (p < 0.05) in ME group, as compared to LE and HE groups on d 60. The expression level of growth hormone receptor (GHR) was decreased (p < 0.001) and IGF-1 was increased with the increase in the dietary energy level. The relative expression of insulin-like growth factor binding protein 3 (IGFBP-3) was higher (p < 0.001) in ME and HE groups, except the LE group. In conclusion, our findings provide a first insight into the combined effect of GH and IGF-1 in controlling the metabolism and productivity of yak. It also showed that medium energy level diet contributed to promote growth performance of yak during the cold season.

Objective: To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects.Design: IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively.Results: Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction.Conclusion: Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity. [ABSTRACT FROM AUTHOR]

We present a novel procedure to monitor the fluctuations of the levels of IGF-1 in capillary blood in the framework of doping control analysis. Being an endogenous hormone, direct methods are not applicable, so the most effective way to detect the intake of the exogenous hormone would be based on the longitudinal monitoring of the athlete. We have therefore followed the individual variability, in four subjects (two males and two females), of the levels of IGF-1 in capillary blood samples collected three times per day for five days, then once a week for at least two months. Analyses were performed by liquid chromatography coupled to tandem mass spectrometry following a bottom-up approach. The whole protocol, from the sample collection to the instrumental analysis, was validated according to the World Anti-Doping Agency's guidelines and ISO17025. The analytical protocol showed to be fit for purpose in terms of sensitivity (LOD 25 ng/mL and LOI 35 ng/mL), selectivity (no interferences were detected at the retention time of IGF-1 and the internal standard), and repeatability (CV<10%). The linearity was confirmed in the range of 50–1000 ng/mL (correlation coefficient R2 >0.995, with a % relative bias of the experimental concentration of the different calibrators used for the estimation of the linearity lower than 20% for the lowest level and than 15% for the other levels). Stability studies were also performed, also to establish the optimal conditions for transport and storage: samples were stable at 4 °C for up to 72 h and at −20 °C and −80 °C for up to three months. Our preliminary results indicate that, in all subjects, the levels of IGF-1 did not present significant circadian fluctuations and remained stable during the entire period of the study (2–3 months, depending on the subject). The stability over time of IGF-1 levels in capillary blood indicates the possibility of detecting the intake of the non-endogenous hormone based on a longitudinal approach, as it is modeled in the framework of the endocrinological module of the athlete biological passport. [Display omitted] • Capillary blood sampling is proposed for the analysis in the antidoping field. • A method for quantifying IGF-1 using a bottom-up approach is presented. • The method was successfully used to quantify IGF-1 levels in volunteers. • Individual variability of IGF-1 levels in capillary plasma was measured. • Longitudinal monitoring IGF-1 levels in capillary blood can allow to detect its abuse. [ABSTRACT FROM AUTHOR]

Acne is a manifestation of hormonal overstimulation of the pilosebaceous units of genetically susceptible individuals. Endogenous reproductive and growth hormones, exogenous reproductive hormones, insulin and endogenous insulin-like growth hormone-1, sourced from and stimulated by dairy and high glycemic load foods, all appear to contribute to this overstimulation. A postulated molecular mechanism linking food and acne is reported and integrated into the clinical picture.