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Search Results to Kenneth S. Polonsky

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overview My laboratory is interested in the role of abnormal insulin secretion in the pathogenesis of type 2 diabetes. We are currently using mouse models of diabetes to define the mechanisms of ß-cell dysfunction. Pancreatic ß-cell death is a very important mechanism contributing to reduced insulin secretion in diabetes. Using Pdx1 deficiency as the experimental model we have determined that all three forms of programmed cell death autophagy, apoptosis and programmed necrosis all contribute to the loss of beta cell mass. We are currently exploring novel approaches to interrupting these pathways. These studies have focused on the role of the BH3-only molecules Puma and Bim in mediating pancreatic ß-cell death. We have demonstrated that reducing expression of Puma and Bim reduces apoptosis of the pancreatic ß-cell in different diabetes models leading to an enhancement of insulin secretion, an increase in ß-cell mass and a lowering of blood glucose.

One or more keywords matched the following items that are connected to Polonsky, Kenneth

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Concept Apoptosis
Concept Apoptosis Regulatory Proteins
Academic Article Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.
Academic Article Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+ stores and arachidonic acid metabolism.
Academic Article Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion.
Academic Article Increased islet apoptosis in Pdx1+/- mice.
Academic Article RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets.
Academic Article Visualizing superoxide production in normal and diabetic rat islets of Langerhans.
Academic Article Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells.
Academic Article Reduced expression of the insulin receptor in mouse insulinoma (MIN6) cells reveals multiple roles of insulin signaling in gene expression, proliferation, insulin content, and secretion.
Academic Article Sustained expression of hepatocyte nuclear factor-6 leads to loss of pancreatic beta-cells by apoptosis.
Academic Article Suppressed insulin signaling and increased apoptosis in CD38-null islets.
Academic Article Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic ß cell death and diabetes.
Academic Article Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis.
Academic Article Pdx1 and other factors that regulate pancreatic beta-cell survival.
Academic Article Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome.
Academic Article Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivation.
Academic Article Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency.
Academic Article Role of BH3-only molecules Bim and Puma in ß-cell death in Pdx1 deficiency.
Academic Article BH3-only molecule Bim mediates ß-cell death in IRS2 deficiency.
Academic Article Pancreatic ß-Cell Death due to Pdx-1 Deficiency Requires Multi-BH Domain Protein Bax but Not Bak.

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  • Apoptosis