26 results on '"Neil Portwood"'
Search Results
2. aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
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Per Antonson, Marko Matic, Neil Portwood, Raoul V Kuiper, Galyna Bryzgalova, Hui Gao, Sara H Windahl, Patricia Humire, Claes Ohlsson, Per-Olof Berggren, Jan-Åke Gustafsson, and Karin Dahlman-Wright
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Medicine ,Science - Abstract
In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERα(flox/flox) mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERα(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ERα(flox/flox) female mice were infertile. In line with this, aP2-Cre/ERα(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERα(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERα(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERα(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.
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- 2014
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3. Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action.
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Marko Matic, Galyna Bryzgalova, Hui Gao, Per Antonson, Patricia Humire, Yoko Omoto, Neil Portwood, Camilla Pramfalk, Suad Efendic, Per-Olof Berggren, Jan-Åke Gustafsson, and Karin Dahlman-Wright
- Subjects
Medicine ,Science - Abstract
An increasing body of evidence now links estrogenic signalling with the metabolic syndrome (MS). Despite the beneficial estrogenic effects in reversing some of the MS symptoms, the underlying mechanisms remain largely undiscovered. We have previously shown that total estrogen receptor alpha (ERα) knockout (KO) mice exhibit hepatic insulin resistance. To determine whether liver-selective ablation of ERα recapitulates metabolic phenotypes of ERKO mice we generated a liver-selective ERαKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERα selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ERα action may not be the responsible factor for the previously identified hepatic insulin resistance in ERαKO mice.
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- 2013
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4. Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice.
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Zuheng Ma, Catharina Lavebratt, Malin Almgren, Neil Portwood, Lars E Forsberg, Robert Bränström, Erik Berglund, Sture Falkmer, Frank Sundler, Nils Wierup, and Anneli Björklund
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Medicine ,Science - Abstract
BACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of β-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K(+) channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. METHODOLOGY/PRINCIPAL FINDINGS:Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wild-type mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the β-cell population and also to α- and δ-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse β-cells. This duration effect on action potential in β-cells from mceph/mceph mice was mimicked by dendrotoxin-K in β-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. CONCLUSION/SIGNIFICANCE:Kv1.1 channels are expressed in the β-cells of several species, and these channels can influence glucose-stimulated insulin release.
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- 2011
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5. The estrogen receptor α-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice: potential molecular mechanisms
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Dana Galuska, S. Efendic, Susann Fält, Galina Bryzgalova, Hui Gao, Juleen R. Zierath, Kurt D. Berndt, Jan-Åke Gustafsson, Andrea Dicker, Akhtar Khan, Lovisa Lundholm, Neil Portwood, and Karin Dahlman-Wright
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Agonist ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,medicine.drug_class ,medicine.medical_treatment ,Glucose uptake ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Adipose tissue ,Estrogen receptor ,Mice, Obese ,Biology ,Carbohydrate metabolism ,Pyrazole ,In Vitro Techniques ,Polymerase Chain Reaction ,chemistry.chemical_compound ,Islets of Langerhans ,Mice ,Endocrinology ,Phenols ,Internal medicine ,Glucose Intolerance ,medicine ,Animals ,heterocyclic compounds ,Muscle, Skeletal ,Oligonucleotide Array Sequence Analysis ,Glucose tolerance test ,medicine.diagnostic_test ,Estradiol ,Insulin ,Body Weight ,Estrogen Receptor alpha ,Computational Biology ,Glucose Tolerance Test ,chemistry ,Adipose Tissue ,Liver ,Glucose-6-Phosphatase ,Pyrazoles ,Triol ,Female ,Estrogen receptor alpha - Abstract
The aim of this study was to validate the role of estrogen receptor α (ERα) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERα-selective agonist propyl pyrazole triol (PPT) or 17β-estradiol (E2) in ob/ob mice. Female ob/ob mice were treated with PPT, E2 or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E2 treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E2 treatment. However, PPT and E2 had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E2 treatment. In the liver, treatment with E2 and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERα.
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- 2020
6. Activation of hepatic AMPK by 17β-estradiol suppresses both nuclear receptor Nr2c2/TR4 and its downstream lipogenic targets, reduces gluconeogenic genes and improves insulin signaling
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Saad Misfer Al-Qahtani, Galyna Bryzgalova, Suad Efendić, Per-Olof Berggren, and Neil Portwood
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AMPK ,lcsh:R5-920 ,17β-estradiol (E2) ,insulin resistance ,lcsh:R ,lcsh:Medicine ,Menopause ,lcsh:Medicine (General) ,insulin signaling ,lipogenesis - Abstract
Estrogen replacement reduces the frequency of type 2 diabetes (T2D), an effect which involves the suppression of hepatic glucose production. The objective of this study was to identify the hepatic mechanisms involved in the beneficial effects of 17β-estradiol (E2) on insulin sensitivity in mice exposed to long term (10 months) high fat diet (HFD) feeding. E2 treatment in HFD mice led to significant improvements in glycemic control. In the livers from these animals, Western blotting studies showed that E2 treatment led to significant increases in the activation state of the AMP-activated protein kinase (AMPK), in association with reduction of the nuclear receptor Nr2c2/TR4 both mRNA and protein levels, and suppression of downstream lipogenic gene expression. These effects were in parallel with up-regulation of hormone sensitive lipase (lipe) expression by E2. Increased fasting glucose levels following HFD feeding were associated with increases in the expression levels of the gluconeogenic genes, g6pt1 and pyruvate carboxylase, whilst E2 treatment significantly reduced their expression levels. The insulin signaling pathway was studied in the liver after acute insulin intervention. The phosphorylation states of AKT2 and FOXO1 were both decreased in HFD mice, and E2 treatment reversed these changes. In conclusion, E2 treatment reduced body weight and improved glycemic control in association with activation of hepatic AMPK, reduced expression of its downstream target Nr2c2/TR4, and consequent decreases in lipogenic gene expression. Together with increased triglyceride mobilization, these changes paralleled improved hepatic insulin signaling and reduced gluconeogenic gene expression. [Dis Mol Med 2016; 4(4.000): 55-67]
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- 2016
7. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression
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Saad Misfer Al-Qahtani, Marion Korach-André, Galyna Bryzgalova, Per Olof Berggren, Karin Dahlman-Wright, Neil Portwood, Suad Efendic, and Ismael Valladolid-Acebes
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0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Adipokine ,Adipose tissue ,030209 endocrinology & metabolism ,Intra-Abdominal Fat ,Diet, High-Fat ,Real-Time Polymerase Chain Reaction ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Adipocyte ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,Obesity ,RNA, Messenger ,Molecular Biology ,Oligonucleotide Array Sequence Analysis ,Adipogenesis ,Leptin receptor ,Estradiol ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,General Medicine ,DNA Methylation ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Adipose triglyceride lipase ,Lipogenesis ,Female ,Insulin Resistance ,Biomarkers - Abstract
Both functional ovaries and estrogen replacement therapy (ERT) reduce the risk of type 2 diabetes (T2D). Understanding the mechanisms underlying the antidiabetic effects of 17β-estradiol (E2) may permit the development of a molecular targeting strategy for the treatment of metabolic disease. This study examines how the promotion of insulin sensitivity and weight loss by E2 treatment in high-fat-diet (HFD)-fed mice involve several anti-adipogenic processes in the visceral adipose tissue. Magnetic resonance imaging (MRI) revealed specific reductions in visceral adipose tissue volume in HFD+E2 mice, compared with HFD mice. This loss of adiposity was associated with diminished visceral adipocyte size and reductions in expression of lipogenic genes, adipokines and of the nuclear receptor nr2c2/tr4. Meanwhile, expression levels of adipose triglyceride lipase/pnpla2 and leptin receptor were increased. As mRNA levels of stat3, a transcription factor involved in brown adipose tissue differentiation, were also increased in visceral adipose, the expression of other brown adipose-specific markers was assessed. Both expression and immunohistochemical staining of ucp-1 were increased, and mRNA levels of dio-2, and of adrβ3, a regulator of ucp-1 expression during the thermogenic response, were increased. Furthermore, expression of cpt-1b, a brown adipose-specific gene involved in fatty acid utilization, was also increased. Methylation studies demonstrated that the methylation status of both dio-2 and adrβ3 was significantly reduced. These results show that improved glycemic control and weight loss due to E2 involve anti-adipogenic mechanisms which include suppressed lipogenesis and augmented fatty acid utilization, and in addition, the activation of brown adipose tissue-specific gene expression in association with E2-dependent epigenetic modifications in these genes.
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- 2016
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8. Estrogen Signalling and the Metabolic Syndrome: Targeting the Hepatic Estrogen Receptor Alpha Action
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Yoko Omoto, Per Antonson, Camilla Pramfalk, Marko Matic, Neil Portwood, Patricia Humire, Suad Efendic, Karin Dahlman-Wright, Per Olof Berggren, Hui Gao, Galyna Bryzgalova, and Jan-Ake Gustafsson
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medicine.medical_specialty ,medicine.drug_class ,lcsh:Medicine ,Diet, High-Fat ,Mice ,Internal medicine ,medicine ,Animals ,Insulin ,lcsh:Science ,Metabolic Syndrome ,Mice, Knockout ,Multidisciplinary ,business.industry ,Body Weight ,lcsh:R ,Estrogen Receptor alpha ,Correction ,Estrogens ,medicine.disease ,Mice, Inbred C57BL ,Endocrinology ,Signalling ,Glucose ,Action (philosophy) ,Liver ,Estrogen ,lcsh:Q ,Metabolic syndrome ,business ,Transcriptome ,Estrogen receptor alpha ,Signal Transduction - Abstract
An increasing body of evidence now links estrogenic signalling with the metabolic syndrome (MS). Despite the beneficial estrogenic effects in reversing some of the MS symptoms, the underlying mechanisms remain largely undiscovered. We have previously shown that total estrogen receptor alpha (ERα) knockout (KO) mice exhibit hepatic insulin resistance. To determine whether liver-selective ablation of ERα recapitulates metabolic phenotypes of ERKO mice we generated a liver-selective ERαKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERα selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ERα action may not be the responsible factor for the previously identified hepatic insulin resistance in ERαKO mice.
- Published
- 2019
9. Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
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Lovisa Lundholm, Neil Portwood, Karin Dahlman-Wright, Suad Efendic, Akhtar Khan, Jan-Ake Gustafsson, and Galyna Bryzgalova
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Leptin ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Gene Expression ,Adipokine ,Adipose tissue ,White adipose tissue ,Biology ,Transfection ,Mice ,Insulin resistance ,Adipokines ,Physiology (medical) ,Internal medicine ,Glucose Intolerance ,Weight Loss ,Adipocytes ,medicine ,Animals ,Hypoglycemic Agents ,Insulin ,Resistin ,Obesity ,Triglycerides ,Glucose tolerance test ,Estradiol ,medicine.diagnostic_test ,Adiponectin ,Reverse Transcriptase Polymerase Chain Reaction ,Fatty Acids ,nutritional and metabolic diseases ,Articles ,Glucose Tolerance Test ,medicine.disease ,Dietary Fats ,Mice, Inbred C57BL ,Endocrinology ,Adipose Tissue ,Liver ,lipids (amino acids, peptides, and proteins) ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17β-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E2, given daily (50 μg/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor α and SREBP1c were not changed by E2treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.
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- 2008
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10. Expression of Glucose-6-phosphatase System Genes in Murine Cortex and Hypothalamus
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B.-H. Goh, A. Khan, Neil Portwood, and Suad Efendic
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Gene isoform ,G6PC ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Protein subunit ,Clinical Biochemistry ,Hypothalamus ,Mice, Obese ,Biology ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Phosphates ,Cerebellar Cortex ,Mice ,chemistry.chemical_compound ,Endocrinology ,Catalytic Domain ,Cortex (anatomy) ,Internal medicine ,medicine ,Animals ,Homeostasis ,Glucose homeostasis ,Regulation of gene expression ,Biochemistry (medical) ,General Medicine ,Isoenzymes ,Glucose ,medicine.anatomical_structure ,Liver ,Glucose 6-phosphate ,chemistry ,Organ Specificity ,Glucose-6-Phosphatase ,biology.protein ,Glucose 6-phosphatase - Abstract
The glucose-6-phosphatase (G6Pase) system participates in the regulation of glucose homeostasis by converting glucose-6-phosphate (G6P) into glucose and inorganic phosphates. We have used an RT-PCR-based cloning and sequencing approach to study the expression of components of the G6Pase system in the hypothalamus and cortex tissues of the ob/ob mouse. We observed the expression of hepatic G6Pase catalytic subunit, G6PC, in both tissues, although increased template inputs were required for its detection. Conversely, expression of both the mouse homologue of the previously-described brain-specific G6P translocase T1 (G6PT1) variant and of the hepatic G6PT1 isoform was easily detectable in hypothalamus and cortex tissues. Of the proposed G6Pase catalytic subunit homologues, the expression of murine ubiquitous G6Pase catalytic subunit-related protein (UGRP, G6PC3) was also easily detectable in both tissues. However, islet-specific G6Pase catalytic subunit-related protein (IGRP, G6PC2) was expressed in a tissue-specific manner, and was detectable only in hypothalamus tissue at increased template inputs. We conclude that cells within ob/ob mouse hypothalamus and cortex tissues express genes with either established or proposed roles in G6P hydrolysis.
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- 2006
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11. Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic β-cells
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Sergei Zaitsev, Neil Portwood, S. Efendic, Vladimir V. Sharoyko, Irina I. Zaitseva, Per Olof Berggren, Mark Varsanyi, Ingo B. Leibiger, and Barbara Leibiger
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Male ,medicine.medical_specialty ,G protein ,medicine.medical_treatment ,Biophysics ,Down-Regulation ,Imidazoline receptor ,Biochemistry ,Islets of Langerhans ,chemistry.chemical_compound ,GTP-Binding Proteins ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Insulin ,RNA, Messenger ,Rats, Wistar ,Imidazolines ,Molecular Biology ,Cells, Cultured ,Monomeric GTP-Binding Proteins ,geography ,geography.geographical_feature_category ,Chemistry ,Pancreatic islets ,RNA ,Cell Biology ,Transfection ,Islet ,Efaroxan ,Rats ,Endocrinology ,medicine.anatomical_structure - Abstract
The monomeric G-protein, Rhes, is a candidate imidazoline-regulated molecule involved in mediating the insulin secretory response to efaroxan [S.L. Chan, L.K. Monks, H. Gao, P. Deaville, N.G. Morgan, Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell, Br. J. Pharmacol. 136 (1) (2002) 31-36]. This suggestion was based on observations regarding changes in Rhes mRNA expression in rat islets and pancreatic beta-cells after prolonged culture with efaroxan, leading to desensitization of the insulin response to the compound. To verify this report, we have evaluated the effects of the imidazoline compounds efaroxan and BL11282 on Rhes mRNA expression in isolated rat pancreatic islets maintained in conditions identical to those used by Chan et al. The results demonstrate that desensitization of the insulin response to efaroxan, or to another imidazoline, BL11282, does not change Rhes mRNA expression levels. Transfection of MIN6 cells with plasmids containing Rhes or Rhes-antisense also does not alter efaroxan- or BL11282-induced insulin secretion. Together, these data do not support the hypothesis that Rhes is an imidazoline-regulated protein.
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- 2005
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12. Overview of Incretin Hormones
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Neil Portwood and S. Efendic
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endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Molecular Sequence Data ,Clinical Biochemistry ,Incretin ,Gastric Inhibitory Polypeptide ,Type 2 diabetes ,Biochemistry ,Glucagon ,Islets of Langerhans ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Insulin Secretion ,Insulin response ,medicine ,Humans ,Insulin ,Secretion ,Amino Acid Sequence ,Protein Precursors ,Gastric emptying ,Chemistry ,digestive, oral, and skin physiology ,Biochemistry (medical) ,General Medicine ,medicine.disease ,Peptide Fragments ,Diabetes Mellitus, Type 2 ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Incretins are hormones released by nutrients from the GI tract. They amplify glucose-induced insulin release. By raising circulating incretin levels, oral glucose provokes a higher insulin response than that resulting from intravenous glucose. The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). In patients with type 2 diabetes, the incretin effect is decreased, mainly due to loss of the GIP-regulated second phase of insulin secretion, and because of a decreased secretion of GLP-1. In addition to its insulinotropic effect, GLP-1 inhibits glucagon release, prolongs gastric emptying, and leads to decreases in body-weight, all of which explain the marked antidiabetogenic effect of this incretin hormone.
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- 2004
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13. Aged Transgenic Mice With Increased Glucocorticoid Sensitivity in Pancreatic β-Cells Develop Diabetes
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Akhtar Khan, Neil Portwood, Thomas Heiden, Martina Kvist Reimer, Suad Efendic, Claes-Göran Östenson, Sam Okret, Bo Ahrén, Galina Bryzgalova, and Behrous Davani
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Blood Glucose ,Aging ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,medicine.medical_treatment ,Mice, Transgenic ,Biology ,Impaired glucose tolerance ,Islets of Langerhans ,Mice ,Glucocorticoid Sensitivity ,Glucocorticoid receptor ,Reference Values ,Internal medicine ,Insulin Secretion ,Internal Medicine ,medicine ,Animals ,Insulin ,Promoter Regions, Genetic ,Glucocorticoids ,Glucose tolerance test ,medicine.diagnostic_test ,Body Weight ,Glucose Tolerance Test ,medicine.disease ,Rats ,Insulin oscillation ,Endocrinology ,Diabetes Mellitus, Type 2 ,Glucocorticoid ,medicine.drug - Abstract
Glucocorticoids are diabetogenic hormones because they decrease glucose uptake, increase hepatic glucose production, and inhibit insulin release. To study the long-term effects of increased glucocorticoid sensitivity in beta-cells, we studied transgenic mice overexpressing the rat glucocorticoid receptor targeted to the beta-cells using the rat insulin I promoter. Here we report that these mice developed hyperglycemia both in the fed and the overnight-fasted states at 12-15 months of age. Progression from impaired glucose tolerance, previously observed in the same colony at the age of 3 months, to manifest diabetes was not associated with morphological changes or increased apoptosis in the beta-cells. Instead, our current results suggest that the development of diabetes is due to augmented inhibition of insulin secretion through alpha(2)-adrenergic receptors (alpha(2)-ARs). Thus, we found a significantly higher density of alpha(2)-ARs in the islets of transgenic mice compared with controls, based on binding studies with the alpha(2)-AR agonist UK 14304. Furthermore, incubation of islets with benextramine, a selective antagonist of the alpha(2)-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets. These results indicate that the chronic enhancement of glucocorticoid signaling in pancreatic beta-cells results in hyperglycemia and impaired glucose tolerance. This effect may involve signaling pathways that participate in the regulation of insulin secretion via the alpha(2)-AR.
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- 2004
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14. Evidence for the expression of both the hydrolase and translocase components of hepatic glucose-6-phosphatase in murine pancreatic islets
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Bee-Hoon Goh, Neil Portwood, Suad Efendic, and Akhtar Khan
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endocrine system ,Monosaccharide Transport Proteins ,Transcription, Genetic ,medicine.medical_treatment ,Protein subunit ,Molecular Sequence Data ,Phosphatase ,Biophysics ,Mice, Obese ,Biochemistry ,Antiporters ,Cell Line ,Islets of Langerhans ,Mice ,Catalytic Domain ,Complementary DNA ,medicine ,Animals ,Translocase ,Molecular Biology ,geography ,geography.geographical_feature_category ,Base Sequence ,biology ,Pancreatic islets ,Insulin ,Proteins ,Cell Biology ,Islet ,Protein Subunits ,medicine.anatomical_structure ,Liver ,Glucose-6-Phosphatase ,biology.protein ,Sequence Alignment ,Glucose 6-phosphatase - Abstract
Glucose-6-phosphatase (G6Pase) is a multicomponent enzyme system which regulates the catalysis of glucose-6-phosphate (G6P) to glucose and inorganic phosphate. G6Pase can antagonize glucose phosphorylation, a step prerequisite in the regulation of insulin secretion from pancreatic beta cells, and G6Pase activity is increased in islets isolated from animal models of type II diabetes. Using RT-PCR with hepatic G6Pase catalytic subunit primers, we demonstrate that the sizes of amplified products from ob/ob mouse islets are identical to those from liver cDNA. This was confirmed by PCR-based cloning and sequencing of the hepatic G6Pase catalytic subunit open reading frame from islet cDNA. The expression in islets of the G6P transporter, G6PT1, was also demonstrated, suggesting that all of the identified hepatic G6Pase system genes are expressed in pancreatic islets. Finally, the expression of islet-specific G6Pase-related protein (IGRP) in pancreatic islets was confirmed and its expression in liver was also observed.
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- 2003
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15. aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra
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Hui Gao, Patricia Humire, Per Olof Berggren, Jan-Åke Gustafsson, Marko Matic, Raoul Kuiper, Neil Portwood, Claes Ohlsson, Galyna Bryzgalova, Karin Dahlman-Wright, Sara H Windahl, and Per Antonson
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Anatomy and Physiology ,Mouse ,Uterus ,Adipose tissue ,Veterinary Anatomy and Physiology ,Mice ,Endocrinology ,Reproductive Physiology ,Molecular Cell Biology ,Mice, Knockout ,Multidisciplinary ,Estradiol ,food and beverages ,Animal Models ,Up-Regulation ,medicine.anatomical_structure ,Letrozole ,Medicine ,Female ,Infertility, Female ,Research Article ,Genetically modified mouse ,medicine.medical_specialty ,medicine.drug_class ,Science ,Estrous Cycle ,Endocrine System ,Biology ,Fatty Acid-Binding Proteins ,Fatty acid-binding protein ,Model Organisms ,Internal medicine ,FLOX ,Nitriles ,medicine ,Genetics ,Animal Genital Anatomy ,Animals ,Reproductive Endocrinology ,Aromatase inhibitor ,Integrases ,Endocrine Physiology ,Estrogen Receptor alpha ,Reproductive System ,Triazoles ,Estrogen ,Veterinary Science ,Gene Function ,Estrogen receptor alpha ,Gene Deletion - Abstract
In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERα(flox/flox) mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERα(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ERα(flox/flox) female mice were infertile. In line with this, aP2-Cre/ERα(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERα(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERα(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERα(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.
- Published
- 2013
16. Effects of a low-intensity electromagnetic field on fibroblast migration and proliferation
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Neil Portwood, Boris Aranovitch, Vivekananda Gupta Sunkari, and Andrej Nikoshkov
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Electromagnetic field ,Vascular Endothelial Growth Factor A ,animal structures ,Biophysics ,Medicine (miscellaneous) ,Fibroblast growth factor ,Fibroblast migration ,In vitro model ,Electromagnetic Fields ,Cell Movement ,medicine ,Humans ,Fibroblast ,Cells, Cultured ,Cell Proliferation ,Regulation of gene expression ,Wound Healing ,Chemistry ,Water ,Dose-Response Relationship, Radiation ,General Medicine ,Fibroblasts ,Thymidine incorporation ,medicine.anatomical_structure ,Gene Expression Regulation ,Immunology ,Fibroblast Growth Factor 1 ,Wound healing - Abstract
The aim of this study was to test if an extremely weak 1 GHz electromagnetic field (EMF), known to be in resonance with clusters of water molecules, has biological effects on human fibroblasts. We demonstrated that in an in vitro model of wound healing, this EMF can activate fibroblast migration. [(3)H]thymidine incorporation experiments demonstrated that the EMF could also activate fibroblast proliferation. Activation of the expression of human fibroblast growth factor 1 (HFGF1) after EMF exposure showed that molecular wound healing pathways are activated in response to this water-resonant EMF.
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- 2011
17. Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice
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Erik Berglund, Zuheng Ma, Robert Bränström, Nils Wierup, Anneli Björklund, Catharina Lavebratt, Malin Almgren, Lars Forsberg, Frank Sundler, Sture Falkmer, and Neil Portwood
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Blood Glucose ,Male ,medicine.medical_treatment ,lcsh:Medicine ,Action Potentials ,Gene Knockout Techniques ,Mice ,Shab Potassium Channels ,Endocrinology ,Insulin-Secreting Cells ,Insulin Secretion ,Insulin ,Pancreatic islet function ,lcsh:Science ,Sequence Deletion ,Membrane potential ,education.field_of_study ,Multidisciplinary ,geography.geographical_feature_category ,Data Collection ,Islet ,Molecular Imaging ,Perfusion ,medicine.anatomical_structure ,Medicine ,Female ,Fura-2 ,Research Article ,medicine.medical_specialty ,Population ,Dendrotoxin ,Biology ,complex mixtures ,Species Specificity ,Internal medicine ,medicine ,Animals ,Humans ,RNA, Messenger ,education ,Diabetic Endocrinology ,geography ,Pancreatic islets ,lcsh:R ,Body Weight ,Wild type ,Rats ,Gene Expression Regulation ,nervous system ,lcsh:Q ,Kv1.1 Potassium Channel ,Cell and Molecular Biology - Abstract
Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the beta-cell population and also to alpha-and delta-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse beta-cells. This duration effect on action potential in beta-cells from mceph/mceph mice was mimicked by dendrotoxin-K in beta-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. Conclusion/Significance: Kv1.1 channels are expressed in the beta-cells of several species, and these channels can influence glucose-stimulated insulin release. (Less)
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- 2011
18. Activation of hepatic AMPK by 17beta-estradiol suppresses both nuclear receptor Nr2c2/TR4 and its downstream lipogenic targets, reduces gluconeogenic genes and improves insulin signaling
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Neil Portwood, S. Efendic, Per Olof Berggren, Galyna Bryzgalova, and Saad Misfer Al-Qahtani
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medicine.medical_specialty ,biology ,Chemistry ,Insulin ,medicine.medical_treatment ,AMPK ,FOXO1 ,Hormone-sensitive lipase ,medicine.disease ,Insulin receptor ,Insulin resistance ,Endocrinology ,Triglyceride mobilization ,Internal medicine ,Lipogenesis ,medicine ,biology.protein - Abstract
Estrogen replacement reduces the frequency of type 2 diabetes (T2D), an effect which involves the suppression of hepatic glucose production. The objective of this study was to identify the hepatic mechanisms involved in the beneficial effects of 17β-estradiol (E2) on insulin sensitivity in mice exposed to long term (10 months) high fat diet (HFD) feeding. E2 treatment in HFD mice led to significant improvements in glycemic control. In the livers from these animals, Western blotting studies showed that E2 treatment led to significant increases in the activation state of the AMP-activated protein kinase (AMPK), in association with reduction of the nuclear receptor Nr2c2/TR4 both mRNA and protein levels, and suppression of downstream lipogenic gene expression. These effects were in parallel with up-regulation of hormone sensitive lipase (lipe) expression by E2. Increased fasting glucose levels following HFD feeding were associated with increases in the expression levels of the gluconeogenic genes, g6pt1 and pyruvate carboxylase, whilst E2 treatment significantly reduced their expression levels. The insulin signaling pathway was studied in the liver after acute insulin intervention. The phosphorylation states of AKT2 and FOXO1 were both decreased in HFD mice, and E2 treatment reversed these changes. In conclusion, E2 treatment reduced body weight and improved glycemic control in association with activation of hepatic AMPK, reduced expression of its downstream target Nr2c2/TR4, and consequent decreases in lipogenic gene expression. Together with increased triglyceride mobilization, these changes paralleled improved hepatic insulin signaling and reduced gluconeogenic gene expression.
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- 2016
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19. Effects of diazoxide on gene expression in rat pancreatic islets are largely linked to elevated glucose and potentially serve to enhance beta-cell sensitivity
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David Brodin, Neil Portwood, Anneli Björklund, Valdemar Grill, and Zuheng Ma
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Islets of Langerhans ,Downregulation and upregulation ,Internal medicine ,Insulin-Secreting Cells ,Gene expression ,Insulin Secretion ,Internal Medicine ,medicine ,Diazoxide ,Animals ,Insulin ,Beta oxidation ,Fatty acid synthesis ,Oligonucleotide Array Sequence Analysis ,Pancreatic islets ,Metabolism ,Rats ,Endocrinology ,medicine.anatomical_structure ,Glucose ,chemistry ,Gene Expression Regulation ,medicine.drug - Abstract
Diazoxide enhances glucose-induced insulin secretion from beta-cells through mechanisms that are not fully elucidated. Here, we used microarray analysis (Affymetrix) to investigate effects of diazoxide. Pancreatic islets were cultured overnight at 27, 11, or 5.5 mmol/l glucose with or without diazoxide. Inclusion of diazoxide upregulated altogether 211 genes (signal log(2) ratio > or =0.5) and downregulated 200 genes (signal log(2) ratio -0.5 or lower), and 92% of diazoxide's effects (up- and downregulation) were observed only after coculture with 11 or 27 mmol/l glucose. We found that 11 mmol/l diazoxide upregulated 97 genes and downregulated 21 genes. Increasing the glucose concentration to 27 mmol/l markedly shifted these proportions toward downregulation (101 genes upregulated and 160 genes downregulated). At 27 mmol/l glucose, most genes downregulated by diazoxide were oppositely affected by glucose (80%). Diazoxide influenced expression of several genes central to beta-cell metabolism. Diazoxide downregulated genes of fatty acid oxidation, upregulated genes of fatty acid synthesis, and downregulated uncoupling protein 2 and lactic acid dehydrogenase. Diazoxide upregulated certain genes known to support beta-cell functionality, such as NKX6.1 and PDX1. Long-term elevated glucose is permissive for most of diazoxide's effects on gene expression, the proportion of effects shifting to downregulation with increasing glucose concentration. Effects of diazoxide on gene expression could serve to enhance beta-cell functionality during continuous hyperglycemia.
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- 2007
20. Evidence that insulin secretion influences SNAP-25 through proteasomal activation
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Valdemar Grill, Zuheng Ma, Aksel Foss, Anneli Björklund, and Neil Portwood
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Male ,medicine.medical_specialty ,Proteasome Endopeptidase Complex ,Synaptosomal-Associated Protein 25 ,Biophysics ,Nerve Tissue Proteins ,Carbohydrate metabolism ,Biology ,Biochemistry ,Exocytosis ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Islets of Langerhans ,Epoxomicin ,Internal medicine ,Insulin Secretion ,medicine ,Diazoxide ,Syntaxin ,Animals ,Humans ,Insulin ,Secretion ,Molecular Biology ,Cells, Cultured ,Pancreatic islets ,Membrane Proteins ,Cell Biology ,Rats ,Endocrinology ,medicine.anatomical_structure ,Somatostatin ,Glucose ,chemistry ,medicine.drug - Abstract
Regulation of SNARE proteins by glucose in pancreatic islets is complex and insufficiently clarified. We aimed to study effects of glucose per se separate from enhancing effects on exocytosis. A 24h culture of rat islets at elevated glucose (27 mmol/L) increased t-SNARES (SNAP-25, syntaxin) (Western blotting). Co-culture with diazoxide, which inhibits glucose-induced insulin secretion, reversed these effects. Effects on SNAP-25 were similar in human and rat islets. Effects of diazoxide were mimicked by blocking secretion with somatostatin (rat islets). Blocking secretion by cooling abolished both glucose and diazoxide effects on SNAP-25. Total SNAP-25 mRNA as well as isoforms alpha and beta were increased by 24-h elevated glucose. Diazoxide failed to reverse the glucose effects on mRNA. However, effects of diazoxide on SNAP-25 protein were nullified by proteasome inhibitors (ALLN, MG-132, and epoxomicin) but not by lysosomal inhibition (NH(4)Cl). Exocytosis per se modifies SNAREs by a process linked to proteasomal activation.
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- 2005
21. Improved grading of breast adenocarcinomas based on genomic instability
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R. Sennerstam, Uwe J. Roblick, Sören Huwendiek, Carin Östring, Gert Auer, Neil Portwood, Anders Zetterberg, Ulrike Kronenwett, Ayodele Alaiya, and Yudi Pawitan
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Genome instability ,Adult ,Cancer Research ,Pathology ,medicine.medical_specialty ,Cyclin A ,Mammary gland ,Aneuploidy ,Breast Neoplasms ,Biology ,Adenocarcinoma ,Malignancy ,Genomic Instability ,Cyclin E ,medicine ,Humans ,RNA, Messenger ,Grading (tumors) ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Cell Nucleus ,Centrosome ,Ploidies ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Cancer research ,biology.protein ,Female ,Ploidy - Abstract
Numerous investigations have shown that in primary breast adenocarcinomas DNA aneuploidy in contrast to DNA diploidy indicates high malignancy potential. On the basis of the study of 104 breast carcinomas, we describe a subtype of aneuploidy, which demonstrates a low degree of malignancy. In image cytometric DNA histograms, this subtype possessed a low percentage (≤8.8%) of nonmodal DNA values as measured by the stemline scatter index (SSI), which is defined as sum of the percentage of cells in the S-phase region, the G2 exceeding rate and the coefficient of variation of the tumor stemline. The cut point of SSI = 8.8% (P = 0.03) enabled us to also subdivide diploid and tetraploid tumors into clinically low and high malignant variants. One possible reason for aneuploidy is impaired distribution of chromosomes at mitosis caused by numerical or structural centrosome aberrations. Cyclins A and E seem to be involved in centrosome duplication. Real-time quantitative PCR measurements of cyclin A and E transcript levels and immunohistochemical determination of cyclin A protein expression showed statistically significantly increased values in the tumors with a high SSI (>8.8%), compared with those with a low SSI. A pilot study demonstrated centrosomal aberrations in an average of 9.6% of the measured cells in four aneuploid carcinomas with high SSI values and in an average of 2.5% of the cells in three aneuploid and three diploid tumors with low SSI. Our data indicate that the SSI, most likely reflecting the degree of genomic instability, allows additional classifying of the known aneuploid, diploid, and tetraploid categories of primary breast adenocarcinomas into low and high malignant subtypes.
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- 2004
22. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. 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Thornalley, P, Babaei jadidi, R, Karachalias, N, Kupich, C, Ahmed, N, Fowler, A, Baker, A, Starczynski, J, O'Hare, P, Szepietowska, B, Szelachowska, M, Puch, U, Glebocka, A, Quinn, D, Mcternan, C, Bonser, R, Idzior walus, B, Woźniakiewicz, E, Dimitriou, K, Apostolou, O, Kontela, E, Devangelio, E, Gould, E, Serri, O, Roussin, A, Buithieu, J, Mamputu, J, Renier, G, Giordanetti, S, De Amici, E, Poggi, G, Turpini, C, Fratino, P, Garzaniti, A, Banu, I, Paries, J, Roman, G, Negrean, M, Bala, C, Nita, C, Kistorp, C, Gustafsson, F, Chong, A, Lip, G, Galatius, S, Ari, N, Sahilli, M, Ceylan isık, A, Ozansoy, G, Karasu yilmaz, C, Matteucci, E, Rosada, J, Pallini, M, Evangelista, I, Cassetti, G, Giusti, C, Giampietro, O, Capaldo, B, Galderisi, M, Cicala, S, Turco, A, Imbroinise, A, Nosso, G, D'Errico, A, De Divitiis, O, Klimontov, V, Korolyova, E, Jeltova, L, Bondar, I, Tarkun, I, Arslan, B, Canturk, Z, Tarkun, P, Agacdiken, A, Komsuoglu, B, Méneveau, N, Pierre justin, E, Alsayed, M, Sabbah, R, Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
- Subjects
0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
23. Diabetes mellitus due to viruses--some recent developments
- Author
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P. A. Titchener, T. M. Szopa, Neil Portwood, and K. W. Taylor
- Subjects
Picornavirus ,viruses ,Endocrinology, Diabetes and Metabolism ,Molecular Sequence Data ,Coxsackievirus Infections ,Human leukocyte antigen ,Coxsackievirus ,medicine.disease_cause ,Virus ,Islets of Langerhans ,Internal Medicine ,medicine ,Diabetes Mellitus ,Animals ,Humans ,Codon ,Picornaviridae Infections ,biology ,Base Sequence ,Rubella virus ,biology.organism_classification ,Virology ,Enterovirus B, Human ,Virus Diseases ,Immunology ,Enterovirus ,Viral disease ,Beta cell - Abstract
Many different viruses belonging to several genera have the potential to damage beta cells. The mechanisms they employ are varied, and infection may result in either a direct destruction of islets and rapid insulin deficiency, or in a more gradual loss of functioning islets with the onset of diabetes many years later. Several case histories involving extensive cytolysis of beta cells can be directly linked to viral infection, whilst an example of diabetes occurring many years after viral infection is found in individuals who had a congenital infection with rubella virus. Here, the virus induces an autoimmune reaction against beta cells. Autoimmune phenomena have also been observed in islets following infections with viruses other than rubella, and thus activation of autoimmune mechanisms leading to beta-cell destruction may be a relatively frequent occurrence. Recent evidence shows that picornaviruses are not exclusively lytic, and can induce more subtle, long-term changes in beta cells, which may be important in the aetiology of diabetes. The exact mechanisms involved are not known, but it is clear that several viruses can directly inhibit insulin synthesis and induce the expression of other proteins such as interferons, and the HLA antigens. Strain differences in viruses are important since not all variants are tropic for the beta cells. Several laboratories are in the process of identifying the genetic determinants of tropism and diabetogenicity, especially amongst the Coxsackie B (CB) virus group. The sequence of one such diabetogenic CB4 strain virus has been determined. It is clear therefore that there are many viruses with the potential to induce diabetes, and a viral involvement in the pathogenesis of diabetes has been established in some instances. Further research work at both a fundamental and epidemiological level is now urgently needed to define the nature of the interaction of such viruses with the beta cell.
- Published
- 1993
24. Coxsackie B4 virus-induced changes in mouse pancreatic beta-cell mRNAs
- Author
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K. W. Taylor and Neil Portwood
- Subjects
Male ,Coxsackie B4 virus ,biology ,Cell ,Coxsackievirus Infections ,In Vitro Techniques ,biology.organism_classification ,Biochemistry ,Molecular biology ,Enterovirus B, Human ,Islets of Langerhans ,Mice ,medicine.anatomical_structure ,Mice, Inbred DBA ,medicine ,Animals ,Insulin ,RNA, Messenger ,Protein Precursors ,Proinsulin - Published
- 1990
25. Coxsackie B4 viruses with the potential to damage beta cells of the islets are present in clinical isolates
- Author
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D. M. Dronfield, T. M. Szopa, Trevor Ward, Neil Portwood, and K. W. Taylor
- Subjects
Male ,viruses ,Endocrinology, Diabetes and Metabolism ,Biology ,In Vitro Techniques ,medicine.disease_cause ,Virus ,Pathogenesis ,Islets of Langerhans ,Mice ,Diabetes mellitus ,Insulin Secretion ,Internal Medicine ,medicine ,Animals ,Humans ,Insulin ,Tropism ,Enterovirus ,Coxsackie B4 virus ,medicine.disease ,biology.organism_classification ,Virology ,In vitro ,Enterovirus B, Human ,Mice, Inbred DBA ,Beta cell - Abstract
Infections with Coxsackie viruses (especially Coxsackie B4) are thought to be involved in the pathogenesis of diabetes. Many interdependent variables determine the outcome of an infection with a Coxsackie virus, one of them being the tropism of the virus for a specific tissue. The extent to which Beta cell tropic variants of Coxsackie B4 virus occur naturally was assessed. Human isolates of this virus were tested in an in vitro system in which elevated insulin release from infected islets incubated at a non-stimulatory (2 mmol/l) glucose concentration appears to be related to viral attack. Using this technique, 8/24 isolates tested, impaired secretory function in mouse islets. Some strains of Coxsackie B4 virus, therefore, will directly infect mouse islets in vitro leading to changes in islet cell function. In conclusion, these findings confirm that variants of Coxsackie B4 virus with the potential to damage Beta cells occur quite frequently in the natural population. In certain circumstances the damage they inflict on Beta cells may cause destruction of these cells, or precipitate overt diabetes.
- Published
- 1990
26. Differential effect of Coxsackie B4 virus on murine pancreatic islet preproinsulin mRNA and glyceraldehyde-3-phosphate dehydrogenase mRNA
- Author
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Keith W. Taylor, Neil Portwood, and Michael J. Clemens
- Subjects
Male ,Preproinsulin ,medicine.medical_specialty ,Coxsackievirus Infections ,In Vitro Techniques ,Biochemistry ,Islets of Langerhans ,Mice ,Internal medicine ,medicine ,Animals ,Insulin ,RNA, Messenger ,Protein Precursors ,Glyceraldehyde 3-phosphate dehydrogenase ,Messenger RNA ,geography ,geography.geographical_feature_category ,Coxsackie B4 virus ,biology ,Chemistry ,Glyceraldehyde-3-Phosphate Dehydrogenases ,biology.organism_classification ,Islet ,Molecular biology ,Enterovirus B, Human ,Diabetes Mellitus, Type 1 ,Endocrinology ,Mice, Inbred DBA ,biology.protein ,Proinsulin - Published
- 1991
- Full Text
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