scholarly journals IS BETA CELL DYSFUNCTION RESPONSIBLE FOR FLAT GLUCOSE TOLERANCE CURVE IN PRIMARY HYPOTHYROIDISM? (A HYPOTHESIS)

2001 ◽  
Vol 57 (2) ◽  
pp. 120-125
Author(s):  
R PAKHETRA ◽  
MK GARG ◽  
JS SAINI
Keyword(s):  
Glucose Tolerance ◽  
Beta Cell ◽  
Primary Hypothyroidism ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Glucose Tolerance Curve ◽  
Tolerance Curve

433 NEW TRANSGENIC PIG DIABETES MODEL EXPRESSING THE MUTANT Insulinc93S FOR THE STUDY OF THE PANCREATIC BETA CELL DYSFUNCTION

2010 ◽  
Vol 22 (1) ◽  
pp. 373
Author(s):  
S. Renner ◽  
N. Klymiuk ◽  
A. Wuensch ◽  
B. Kessler ◽  
M. Kurome ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Point Mutation ◽  
Genetic Background ◽  
Mutant Mouse ◽  
Pancreatic Beta Cell ◽  
Beta Cell Dysfunction ◽  
Transgenic Pig ◽  
Cell Dysfunction

We previously established a mutant mouse line showing diabetes which was caused by a point mutation in the Insulin 2 (Ins2) gene. The point mutation leads to the amino acid exchange C95S and the loss of the A6-A11 intrachain disulfide bond of insulin. Male heterozygous Ins2C95S mutant mice develop progressive diabetes mellitus with strong reduction of the total pancreatic islet volume and the total beta cell volume together with severe alterations of the beta cell structure. As pigs share many anatomical and physiological characteristics with humans, we aimed to establish a transgenic pig model expressing the mutant insulin by additive gene transfer for the subsequent study of beta cell dysfunction in diabetes mellitus. The transgene consisted of German Landrace insulin sequences including 1.3 kb of the insulin promoter and 1 kb insulin gene sequences with the 3 exons and the T to A (C93S) point mutation in exon 3 analogous to the mutant mouse insulin. A floxed neomycin resistance gene at the 3′ end of the transgene was used as a selection marker. After successful transfection of male fetal fibroblasts of both the German Landrace and the Schwaebisch- Haellisch pig breeds, pooled transgenic fibroblasts were used for somatic cell nuclear transfer (SCNT). Five hundred three reconstructed pig embryos were generated and endoscopically transferred to 5 synchronized recipients. One pregnancy with German Landrace genetic background and one pregnancy with Schwaebisch-Haellisch genetic background of the cloned embryos developed to term, which gave rise to 3 living offspring from each of the 2 pregnancies; 5 of the 6 piglets were transgenic. Southern blot analysis showed different transgene signal patterns in all animals examined. Transgenic pigs of both litters revealed unaltered fasting blood glucose levels up to an age of 8 months. However, disturbed intravenous glucose tolerance and reduced insulin secretion were detected in 1 transgenic pig of the first litter at 8 months of age. The area under the glucose curve of this transgenic pig was 75% larger (22 136 v. 12617) and the area under the insulin curve 53% smaller (1250 v. 2670) compared with the control. Ongoing analyses comprise glucose tolerance tests in the second litter as well as pathohistologic analysis of the pancreata of both litters. Cells from suitable transgenic founders will be used for recloning to establish a new transgenic pig model expressing the mutant InsulinC93S for an in-depth study of pancreatic beta cell dysfunction in diabetes mellitus. Supported by the Deutsche Forschungsgemeinschaft (GRK1029).

scholarly journals The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM

2021 ◽  
Author(s):  
Gareth J. Dunseath ◽  
Stephen D. Luzio ◽  
Rajesh Peter ◽  
David R. Owens
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Glucose Intolerance ◽  
Insulin Response ◽  
Tolerance Test ◽  
Beta Cell Dysfunction ◽  
Newly Diagnosed ◽  
Intravenous Glucose ◽  
Cell Dysfunction

Abstract Aims The two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays. Materials and methods A total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis. Results The MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function. Conclusion This study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.

83-OR: Pancreatic Exocrine to Endocrine Cell Cross Talk Mediates Endoplasmic Reticulum Stress and Beta-Cell Dysfunction in MODY8

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 83-OR
Author(s):  
SEVIM KAHRAMAN ◽  
DANIELLE DIEGISSER ◽  
BENTE B. JOHANSSON ◽  
ANDERS MOLVEN ◽  
ROHIT KULKARNI
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Cross Talk ◽  
Endocrine Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pancreatic Exocrine

Autoimmunity to insulin, beta cell dysfunction, and development of insulin-dependent diabetes mellitus

Diabetes ◽  
1986 ◽  
Vol 35 (2) ◽  
pp. 139-142 ◽  
Author(s):  
S. Srikanta ◽  
A. T. Ricker ◽  
D. K. McCulloch ◽  
J. S. Soeldner ◽  
G. S. Eisenbarth ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Beta Cell ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Insulin Dependent

Comparison of Sleeve Gastrectomy and Conservatory Treatment Effect on Biochemical and Hormonal Profile of Obese Type 2 Diabetes Subjects: CREDOR Randomized Controlled Study Results

2017 ◽  
Vol 68 (7) ◽  
pp. 1622-1627 ◽  
Author(s):  
Diana Simona Stefan ◽  
Andrada Mihai ◽  
Daiana Bajko ◽  
Daniela Lixandru ◽  
Laura Petcu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Control Group ◽  
Cell Dysfunction ◽  
Randomized Controlled

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

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