A. Valera et al., EXPRESSION OF GLUT-2 ANTISENSE RNA IN BETA-CELLS OF TRANSGENIC MICE LEADS TO DIABETES, The Journal of biological chemistry, 269(46), 1994, pp. 28543-28546
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.