Sci. STKE, 24 January 2006
GLUCOSE REGULATION Insulin Increases Sensitivity to GABA
Blood glucose concentrations are regulated by the reciprocal actions of insulin and glucagon, two hormones secreted by β and α cells of the pancreas, respectively. Xu et al. used both glucagon-secreting cultured α cell lines and isolated rat islets to show that insulin stimulated an increase in cell surface abundance of the ionotropic -aminobutyric acid type A (GABAA) receptor, which hyperpolarized the α cells and decreased glucagon secretion. In the isolated rat islets, elevated concentrations of glucose stimulated insulin release without changing GABA release from the β cells and decreased glucagon secretion from the α cells. In cultured cells, GABAA insertion in the plasma membrane required the activity of the phosphoinositide 3-kinase (PI3K) pathway and phosphorylation of the β subunit of the GABAA receptor by Akt. In cells pretreated with glucose and insulin for 24 hours to desensitize the insulin receptor, subsequent application of insulin failed to increase GABAA receptors on the cell surface and failed to inhibit glucagon secretion. This was likely due to the slight elevation in basal Akt activity and increased abundance of GABAA receptors already present on the surface of these chronically stimulated cells. Defects in this pathway may contribute to type II diabetic hyperglycemia.
E. Xu, M. Kumar, Y. Zhang, W. Ju, T. Obata, N. Zhang, S. Liu, A. Wendt, S. Deng, Y. Ebina, M. B. Wheeler, M. Braun, Q. Wang, Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system. Cell Metab. 3, 47-58 (2006). [PubMed]
Citation: Insulin Increases Sensitivity to GABA. Sci. STKE 2006, tw36 (2006).
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