EXPRESSION OF GLUT-2 ANTISENSE RNA IN BETA-CELLS OF TRANSGENIC MICE LEADS TO DIABETES

An insulin response to glucose is required to correct hyperglycemia, T wo proteins, the glucose transporter GLUT-2 and the glucose-phosphoryl ating enzyme glucokinase, have been implicated in the control of gluco se metabolism in beta cells. To study the role of glucose transporter GLUT-2 in the regulation of insulin secretion and in the development o f diabetes mellitus, we have obtained transgenic mice expressing high levels of GLUT-2 antisense RNA in beta cells. Western blot analysis sh owed an 80% reduction in GLUT-2 protein in the beta cells of these ani mals. Islets from transgenic mice showed impaired glucose-stimulated i nsulin secretion. In addition, much higher levels of blood glucose wer e detected in transgenic mice than in controls when glucose tolerance tests were performed. These results suggest that the reduction of GLUT -2 in the pancreas could be a crucial step in the development of diabe tes mellitus.