GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes

Antine E. Stenbit, Tsu Shuen Tsao, Jing Li, Rémy Burcelin, David L. Geenen, Stephen M. Factor, Karen Houseknecht, Ellen B. Katz, Maureen J. Charron

Research output: Contribution to journalArticlepeer-review

299 Scopus citations


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 (GLUT4(+/-)) 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.

Original languageEnglish (US)
Pages (from-to)1096-1101
Number of pages6
JournalNature Medicine
Issue number10
StatePublished - Oct 1997

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes'. Together they form a unique fingerprint.

Cite this