Muscle-specific transgenic complementation of GLUT4-deficient mice: Effects on glucose but not lipid metabolism

Tsu Shuen Tsao, Antine E. Stenbit, Jing Li, Karen L. Houseknecht, Juleen R. Zierath, Ellen B. Katz, Maureen J. Charron

Research output: Contribution to journalArticle

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Abstract

We have taken the approach of introducing the muscle-specific myosin light chain (MLC)-GLUT4 transgene into the GLUT4-null background to assess the relative role of muscle and adipose tissue GLUT4 in the etiology of the GLUT4-null phenotype. The resulting MLC-GLUT4-null mice express GLUT4 predominantly in the fast-twitch extensor digitorum longus (EDL) muscle. GLUT4 is nearly absent in female white adipose tissue (WAT) and slow-twitch soleus muscle of both sexes of MLC-GLUT4-null mice. GLUT4 content in male MLC-GLUT4-null WAT is 20% of that in control mice. In transgenically complemented EDL muscle, 2-deoxyglucose (2-DOG) uptake was restored to normal (male) or above normal (female) levels. In contrast, 2-DOG uptake in slow- twitch soleus muscle of MLC-GLUT4-null mice was not normalized. With the normalization of glucose uptake in fast-twitch skeletal muscle, whole body insulin action was restored in MLC-GLUT4-null mice, as shown by the results of the insulin tolerance test. These results demonstrate that skeletal muscle GLUT4 is a major regulator of skeletal muscle and whole body glucose metabolism. Despite normal skeletal muscle glucose uptake and insulin action, the MLC-GLUT4-null mice exhibited decreased adipose tissue deposits, adipocyte size, and fed plasma FFA levels that are characteristic of GLUT4- null mice. Together these results indicate that the defects in skeletal muscle and whole body glucose metabolism and adipose tissue in GLUT4-null mice arise independently.

Original languageEnglish (US)
Pages (from-to)671-677
Number of pages7
JournalJournal of Clinical Investigation
Volume100
Issue number3
StatePublished - Aug 1 1997

Fingerprint

Myosin Light Chains
Lipid Metabolism
Skeletal Muscle
Glucose
Muscles
Adipose Tissue
White Adipose Tissue
Deoxyglucose
Insulin
Transgenes
Adipocytes
Phenotype

Keywords

  • Glucose metabolism
  • GLUT4
  • Knockout mice
  • Skeletal muscle
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tsao, T. S., Stenbit, A. E., Li, J., Houseknecht, K. L., Zierath, J. R., Katz, E. B., & Charron, M. J. (1997). Muscle-specific transgenic complementation of GLUT4-deficient mice: Effects on glucose but not lipid metabolism. Journal of Clinical Investigation, 100(3), 671-677.

Muscle-specific transgenic complementation of GLUT4-deficient mice : Effects on glucose but not lipid metabolism. / Tsao, Tsu Shuen; Stenbit, Antine E.; Li, Jing; Houseknecht, Karen L.; Zierath, Juleen R.; Katz, Ellen B.; Charron, Maureen J.

In: Journal of Clinical Investigation, Vol. 100, No. 3, 01.08.1997, p. 671-677.

Research output: Contribution to journalArticle

Tsao, TS, Stenbit, AE, Li, J, Houseknecht, KL, Zierath, JR, Katz, EB & Charron, MJ 1997, 'Muscle-specific transgenic complementation of GLUT4-deficient mice: Effects on glucose but not lipid metabolism', Journal of Clinical Investigation, vol. 100, no. 3, pp. 671-677.
Tsao TS, Stenbit AE, Li J, Houseknecht KL, Zierath JR, Katz EB et al. Muscle-specific transgenic complementation of GLUT4-deficient mice: Effects on glucose but not lipid metabolism. Journal of Clinical Investigation. 1997 Aug 1;100(3):671-677.
Tsao, Tsu Shuen ; Stenbit, Antine E. ; Li, Jing ; Houseknecht, Karen L. ; Zierath, Juleen R. ; Katz, Ellen B. ; Charron, Maureen J. / Muscle-specific transgenic complementation of GLUT4-deficient mice : Effects on glucose but not lipid metabolism. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 3. pp. 671-677.
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