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Article
Nature Medicine  3, 1096 - 1101 (1997)
doi:10.1038/nm1097-1096

GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes

Antine E. Stenbit1, Tsu-Shuen Tsao1, Jing Li1, Rémy Burcelin1, David L. Geenen2, 3, Stephen M. Factor2, 4, Karen Houseknecht5, Ellen B. Katz1 & Maureen J. Charron1

  1Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA

  2Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA

  3Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA

  4Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA

  5Department of Animal Sciences, Purdue University, West Lafayette, Indiana 47907, USA

 Correspondence should be addressed to M.J.C.

GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body glucose homeostasis, we disrupted the murine GLUT4 gene by homologous recombination. Male mice heterozygous for the mutation (GLUT +/-) exhibited a decrease in GLUT4 expression in adipose tissue and skeletal muscle. This decrease in GLUT4 expression did not result in obesity but led to increased serum glucose and insulin, reduced muscle glucose uptake, hypertension, and diabetic histopathologies in the heart and liver similar to those of humans with non-insulin-dependent diabetes mellitus (NIDDM). The male GLUT4 +/- mice represent a good model for studying the development of NIDDM without the complications associated with obesity.

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ISSN: 1078-8956
EISSN: 1546-170X
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