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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

Item TypeName
Concept Calcium Signaling
Concept Intercellular Signaling Peptides and Proteins
Concept Signal Transduction
Academic Article Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice.
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 Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion.
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 Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in betaIRKO mice.
Academic Article Hypoglycemic potency and metabolic clearance rate of intravenously administered human proinsulin and metabolites.
Academic Article Suppressed insulin signaling and increased apoptosis in CD38-null islets.
Academic Article Insulin signaling in alpha cells modulates glucagon secretion in vivo.
Academic Article Ginsenoside Re rapidly reverses insulin resistance in muscles of high-fat diet fed rats.
Academic Article Organ alchemy: producing insulin in the liver.
Academic Article Role of BH3-only molecules Bim and Puma in ß-cell death in Pdx1 deficiency.
Academic Article ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
Academic Article ß-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
Academic Article BH3-only molecule Bim mediates ß-cell death in IRS2 deficiency.

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