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

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46 Scopus citations

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
DOIs
Publication statusPublished - Aug 1 1997

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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