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 journalArticle

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Abstract

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
Volume3
Issue number10
DOIs
StatePublished - Oct 1997

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Medical problems
Knockout Mice
Muscle
Insulin Resistance
Insulin
Glucose
Muscles
Obesity
Type 2 Diabetes Mellitus
Adipose Tissue
Glucose Transporter Type 4
Tissue
Homologous Recombination
Liver
Skeletal Muscle
Homeostasis
Genes
Hypertension
Mutation
Serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Stenbit, A. E., Tsao, T. S., Li, J., Burcelin, R., Geenen, D. L., Factor, S. M., ... Charron, M. J. (1997). GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nature Medicine, 3(10), 1096-1101. https://doi.org/10.1038/nm1097-1096

GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. / Stenbit, Antine E.; Tsao, Tsu Shuen; Li, Jing; Burcelin, Rémy; Geenen, David L.; Factor, Stephen M.; Houseknecht, Karen; Katz, Ellen B.; Charron, Maureen J.

In: Nature Medicine, Vol. 3, No. 10, 10.1997, p. 1096-1101.

Research output: Contribution to journalArticle

Stenbit, AE, Tsao, TS, Li, J, Burcelin, R, Geenen, DL, Factor, SM, Houseknecht, K, Katz, EB & Charron, MJ 1997, 'GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes', Nature Medicine, vol. 3, no. 10, pp. 1096-1101. https://doi.org/10.1038/nm1097-1096
Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, Factor SM et al. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nature Medicine. 1997 Oct;3(10):1096-1101. https://doi.org/10.1038/nm1097-1096
Stenbit, Antine E. ; Tsao, Tsu Shuen ; Li, Jing ; Burcelin, Rémy ; Geenen, David L. ; Factor, Stephen M. ; Houseknecht, Karen ; Katz, Ellen B. ; Charron, Maureen J. / GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. In: Nature Medicine. 1997 ; Vol. 3, No. 10. pp. 1096-1101.
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