DEVELOPMENT OF THE INSULIN SECRETORY DEFECT IN GENETICALLY DIABETIC (db/db) MOUSE

1978 ◽  
Vol 87 (3) ◽  
pp. 543-551 ◽  
Author(s):  
Ove Berglund ◽  
Barbara J. Frankel ◽  
Bo Hellman
Keyword(s):  
Body Weight ◽  
Serum Insulin ◽  
Insulin Response ◽  
Serum Glucose ◽  
Pancreatic Β Cell ◽  
Diabetic Mice ◽  
Perfused Pancreas ◽  
Β Cell ◽  
Cell Hyperplasia ◽  
Genetically Diabetic Mice

ABSTRACT Genetically diabetic mice (C57BL/KsJ-db/db) were used as a model to study the development of defects of insulin secretion in relation to common metabolic indicators (body weight, serum glucose and insulin, and islet insulin contant). Consistent with the idea of a protective effect of oestrogen on the pancreatic β-cell, the female diabetic mice survived longer than the males. In males, while serum insulin decreased in the later stages of the disease, serum glucose increased progressively with age. Perfusion of the diabetic pancreases revealed a rise and subsequent fall with age of the basal insulin released at 3 mm glucose. Despite previous reports of β-cell hyperplasia, progressive impairment of the insulin response to 20 mm glucose, or to 20 mm glucose and 1 mm 3-isobutyl-1-methylxanthine, was seen with increasing age in experiments with perfused pancreas or microdissected islets. Islet content of insulin also decreased progressively with age in the diabetic animals.

Effects of cortisol and progesterone on insulin binding and lipogenesis in adipocytes from normal and diabetic rats

1985 ◽  
Vol 106 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A.-M. Mendes ◽  
R. J. Madon ◽  
D. J. Flint
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Insulin Binding ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Receptor Concentration

ABSTRACT Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue. J. Endocr. (1985) 106, 225–231

scholarly journals Effect of metformin on the expression of SNAER proteins in the skeletal muscle of rats with type 2 diabetes

2021 ◽  
pp. 270-278
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Snare Complex ◽  
Snare Proteins ◽  
Glucose Levels ◽  
Male Wistar Rats

Background and Aims: SNARE proteins are composed of a combination of SNAP-23, Stx-4, and VAMP-2 isoforms that are significantly expressed in skeletal muscle. These proteins control the transport of GLUT4 to the cell membranes. The modifications in the expression of SNARE proteins can cause Type 2 diabetes. The present study aimed to assess the effect of metformin on the expression of these proteins in rats. Materials and Methods: For the purpose of the study, 40 male Wistar rats were randomly selected. Streptozotocin and Nicotinamide were used for the induction of type 2 diabetes. The animals were assigned to five groups (n=8), including healthy and diabetic groups as control, as well as three experimental groups which were treated with different doses of metformin (100, 150, and 200 mg/kg body weight) for 30 days. The quantitative reverse transcription PCR (RT-qPCR) method was applied to evaluate the expression of SNARE complex proteins.. Results: Based on the results, metformin (100, 150, and 200 mg/kg body weight) decreased serum glucose levels and increased serum insulin levels. This difference in dose of 200 mg/kg body weight was statistically significant (P<0.05). Moreover, all three doses of metformin increased the expression of SNAP- 23, syntaxin-4, and VAMP-2 proteins in skeletal muscle tissue. Metformin at a dose of 200 mg/kg body weight demonstrated the most significant effects (P<0.05). Conclusion: As evidenced by the results of the current study, another anti-diabetic mechanism of metformin is to increase the expression of SNARE proteins, which effectively improves insulin resistance and lowers blood glucose.

scholarly journals Automated quantification of pancreatic β-cell mass

2014 ◽  
Vol 306 (12) ◽  
pp. E1460-E1467 ◽  
Author(s):  
Maria L. Golson ◽  
William S. Bush ◽  
Marcela Brissova
Keyword(s):  
High Resolution ◽  
Mass Measurement ◽  
Virtual Slide ◽  
Cell Mass ◽  
Automated Analysis ◽  
Systematic Sampling ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Hyperplasia ◽  
Time Required

β-Cell mass is a parameter commonly measured in studies of islet biology and diabetes. However, the rigorous quantification of pancreatic β-cell mass using conventional histological methods is a time-consuming process. Rapidly evolving virtual slide technology with high-resolution slide scanners and newly developed image analysis tools has the potential to transform β-cell mass measurement. To test the effectiveness and accuracy of this new approach, we assessed pancreata from normal C57Bl/6J mice and from mouse models of β-cell ablation (streptozotocin-treated mice) and β-cell hyperplasia (leptin-deficient mice), using a standardized systematic sampling of pancreatic specimens. Our data indicate that automated analysis of virtual pancreatic slides is highly reliable and yields results consistent with those obtained by conventional morphometric analysis. This new methodology will allow investigators to dramatically reduce the time required for β-cell mass measurement by automating high-resolution image capture and analysis of entire pancreatic sections.

scholarly journals HRD1, an Important Player in Pancreatic β-Cell Failure and Therapeutic Target for Type 2 Diabetic Mice

Diabetes ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 940-953 ◽  
Author(s):  
Tijun Wu ◽  
Shuang Zhang ◽  
Jialiang Xu ◽  
Yaqin Zhang ◽  
Tong Sun ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Pancreatic Β Cell ◽  
Diabetic Mice ◽  
Β Cell ◽  
Important Player ◽  
Type 2 Diabetic

Opioid antagonism alters blood glucose homeostasis during exercise in humans

1994 ◽  
Vol 76 (6) ◽  
pp. 2452-2460 ◽  
Author(s):  
M. S. Hickey ◽  
S. W. Trappe ◽  
A. C. Blostein ◽  
B. A. Edwards ◽  
B. Goodpaster ◽  
...  
Keyword(s):  
Serum Insulin ◽  
Insulin Response ◽  
Serum Glucose ◽  
Endogenous Opioid ◽  
Hormonal Responses ◽  
Blood Glucose Homeostasis ◽  
The Difference ◽  
Response To Exercise ◽  
Exercise In Humans

In an attempt to clarify the role of endogenous opioid peptides in substrate mobilization and hormonal responses to dynamic exercise, eight trained cyclists completed exercise trials at 90% of maximal O2 consumption (VO2max) until exhaustion and at 70% VO2max for 90 min. Trials were conducted after intravenous administration of the opiate antagonist naloxone (NAL, 0.1 mg/kg bolus + 0.1 mg.kg-1.h-1) or volume-matched saline (SAL) at each intensity. Serum glucose was maintained at significantly higher levels at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and at all points during exercise and at 30 and 60 min of recovery in the 90%-NAL than in the 90%-SAL trial. The serum insulin response to exercise was not altered by NAL administration at either intensity. Serum C-peptide was approximately 50% higher at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial but was significantly lower during exercise in the 90%-NAL than in the 90%-SAL trial. The plasma glucagon response to exercise at 70% VO2max was not altered by NAL administration but was significantly elevated in the 90%-NAL vs. the 90%-SAL trial. Plasma epinephrine was 50–150% (approximately 2–3 nM) higher during exercise from 30 to 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and was higher at termination (4.9 +/- 2.1 vs. 2.7 +/- 1.7 nM) in the 90%-NAL than in the 90%-SAL trial, although the difference in the 90% trial was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes

2016 ◽  
Vol 311 (2) ◽  
pp. E380-E395 ◽  
Author(s):  
María S. Bianchi ◽  
Stefanía Bianchi ◽  
Andrés Hernado-Insúa ◽  
Leandro M. Martinez ◽  
Néstor Lago ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Autoimmune Diabetes ◽  
Serum Insulin ◽  
Diabetic Mice ◽  
Cell Recovery ◽  
Β Cell ◽  
Diabetes Model ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1

Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cell cloning capacity and reverts toxic diabetes in rats. Here, we evaluated long-term (20 doses) and short-term (2–6 doses) effects of IMT504 (20 mg·kg−1·day−1 sc) in an immunodependent diabetes model: multiple low-dose streptozotocin-injected BALB/c mice (40 mg·kg−1·day−1 ip for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. IMT504 reduced glycemia, induced β-cell recovery, and impaired islet infiltration. IMT504 induced early blood glucose decrease and infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, and increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression; preproi nsulin-2, proglucagon, somatostatin, nestin, regenerating gene-1, and C-X-C motif ligand-1 cytokine ( Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated platelet endothelial cell adhesion molecule- 1 ( Pecam1) in islets from control and diabetic mice, whereas it increased regenerating gene-2 ( Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.

scholarly journals Ameliorative Effect of Hexane Extract ofPhalaris canariensison High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Rosa Martha Perez Gutierrez ◽  
Diana Madrigales Ahuatzi ◽  
Maria del Carmen Horcacitas ◽  
Efren Garcia Baez ◽  
Teresa Cruz Victoria ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
High Fat Diet ◽  
Serum Insulin ◽  
Body Weight Loss ◽  
Insulin Level ◽  
Hexane Extract ◽  
Diabetic Mice ◽  
High Fat ◽  
Obesity And Diabetes

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect ofPhalaris canariensisseeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

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