Response of glutamic acid decarboxylase to glucose but not arginine in islets

This study examined responses of glutamic acid decarboxylase (GAD65) and gamma-aminobutyric acid (GABA) to glucose in pancreatic islets. Islets isolated from Wistar rats were cultured for the three days under different concentrations of glucose (5.6, 11.1 or 16.7 mM) or arginine (2 x 10(-1)-2 x 10(-4) mM) for different periods of time. The expression of GAD65 increased 3.8- and 4.5-fold with the elevation of glucose concentrations as well as the prolongation of culture periods of time, while it did not increase with arginine. GABA content of islets did not change in a range of 5.6 to 16.7 mM glucose. These results suggest that normalization of hyperglycemia would reduce the expression of the autoantigen in islets, which might prevent islets from further destruction. To the contrary, the persistent hyperglycemia could interfere with insulin synthesis not by change of GABA in islets but by the destruction of islets through GAD65 expression.