Altered Expression of Uncoupling Protein 2 in GLP-1-producing Cells after Chronic High Glucose Exposure: Implications for the Pathogenesis of Diabetes Mellitus.

Altered Expression of Uncoupling Protein 2 in GLP-1-producing Cells after Chronic High Glucose Exposure: Implications for the Pathogenesis of Diabetes Mellitus. Am J Physiol Cell Physiol. 2016 Jan 6;:ajpcell.00148.2015 Authors: Urbano F, Filippello A, Di Pino A, Barbagallo D, Di Mauro S, Pappalardo A, Rabuazzo AM, Purrello M, Purrello F, Piro S Abstract Glucagon-like peptide-1 (GLP-1) is a gut L-cell hormone that enhances glucose-stimulated insulin secretion. Several approaches that prevent GLP-1 degradation or activate the GLP-1 receptor are being used to treat type 2 diabetes mellitus (T2DM) patients. In T2DM, GLP-1 secretion has been suggested to be impaired, and this defect appears to be a consequence rather than a cause of impaired glucose homeostasis. However, although defective GLP-1 secretion has been correlated with insulin resistance, little is known about the direct effects of chronic high glucose concentrations, which are typical in diabetes patients, on GLP-1-secreting cell function. In the present study, we demonstrate that glucotoxicity directly affects GLP-1 secretion in GLUTag cells chronically exposed to high glucose. Our results indicate that this abnormality is associated with a decrease in ATP production due to the elevated expression of mitochondrial uncoupling protein 2 (UCP2). Further, UCP2 inhibition using siRNA and the application of glibenclamide, a K(+) ATP channel blocker, reverse the GLP-1 secretion defe...
Source: American Journal of Physiology. Cell Physiology - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research