scholarly journals The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus

2017 ◽  
Vol 26 (10) ◽  
pp. 501-518 ◽  
Author(s):  
Philipp A. Gerber ◽  
Guy A. Rutter
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction

scholarly journals Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets

Diabetologia ◽  
2011 ◽  
Vol 54 (9) ◽  
pp. 2337-2346 ◽  
Author(s):  
D. Favre ◽  
G. Niederhauser ◽  
D. Fahmi ◽  
V. Plaisance ◽  
S. Brajkovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Dysfunction ◽  
Rat Islets ◽  
Cell Dysfunction ◽  
Inducible Camp Early Repressor

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 Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mi-Kyung Kim ◽  
Hye-Soon Kim ◽  
In-Kyu Lee ◽  
Keun-Gyu Park
Keyword(s):  
Diabetes Mellitus ◽  
Endoplasmic Reticulum ◽  
Beta Cell ◽  
Er Stress ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Insulin Biosynthesis ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
The Relationship

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis.

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

Beta Cell Dysfunction, Oxidative Stress and S6K1 Activation in Pancreas in the Zucker Obese Rat Model

2011 ◽  
pp. P2-480-P2-480
Author(s):  
Guido Lastra ◽  
Charles B Krueger ◽  
Camila Manrique ◽  
James R Sowers
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Rat Model ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction

scholarly journals Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Molecular Pathways ◽  
Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

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