Expression of GLUT-2 antisense RNA in β cells of transgenic mice leads to diabetes

Alfons Valera, Gemma Solanes, Josefa Fernández-Alvarez, Anna Pujol, Jorge Ferrer, Guillermina Asins, Ramon Gomis, Fatima Bosch

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78 Citations (Scopus)

Abstract

An insulin response to glucose is required to correct hyperglycemia. Two proteins, the glucose transporter GLUT-2 and the glucose-phosphorylating enzyme glucokinase, have been implicated in the control of glucose metabolism in β cells. To study the role of glucose transporter GLUT-2 in the regulation of insulin secretion and in the development of diabetes mellitus, we have obtained transgenic mice expressing high levels of GLUT-2 antisense RNA in β cells. Western blot analysis showed an 80% reduction in GLUT-2 protein in the β cells of these animals. Islets from transgenic mice showed impaired glucose-stimulated insulin secretion. In addition, much higher levels of blood glucose were 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 diabetes mellitus.
Original languageEnglish
Pages (from-to)28543-28546
JournalJournal of Biological Chemistry
Volume269
Issue number46
Publication statusPublished - 18 Nov 1994

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