GLUT4 HETEROZYGOUS KNOCKOUT MICE DEVELOP MUSCLE INSULIN-RESISTANCE AND DIABETES

GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT I activity is sugg ested to be one of the factors responsible for decreased glucose uptak e in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body glucose homeostasis, we disru pted the murine GLUT4 gene by homologous recombination. Male mice hete rozygous for the mutation (GLUT4(+/-)) exhibited a decrease in GLUT4 e xpression in adipose tissue and skeletal muscle. This decrease in GLUT 4 expression did not result in obesity but led to increased serum gluc ose and insulin, reduced muscle glucose uptake, hypertension, and diab etic histopathologies in the heart and liver similar to those of human s with non-insulin-dependent diabetes mellitus (NIDDM). The male GLUT4 (+/-) mice represent a good model for studying the development of NIDD M without the complications associated with obesity.