Germline manipulation of glucose homeostasis via alteration of glucose transporter levels in skeletal muscle

B. A. Marshall, J. M. Ren, D. W. Johnson, E. M. Gibbs, J. S. Lillquist, W. C. Soeller, J. O. Holloszy, M. Mueckler

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Transgenic mice were constructed that overexpress the human Glut1 glucose transporter in skeletal muscle. Transcription of the human Glut1 cDNA was driven by the rat myosin light chain 2 promoter. Soleus and quadriceps muscles from transgenic mice expressed increased levels of Glut1 protein relative to muscles obtained from nontransgenic littermates, but there was no difference in the level of Glut4 protein between the two groups. Skeletal muscles isolated from the transgenic animals exhibited 3-4 fold increases in basal glucose uptake relative to muscles obtained from nontransgenic littermates. Muscles isolated from nontransgenic littermates exhibited 2-3- fold increases in glucose transport after incubation in the presence of insulin, but no insulin-stimulated increase in transport was observed in the muscles of transgenic mice. Plasma glucose levels were reduced by 18 and 30%, respectively, in fed and fasted transgenic mice relative to their nontransgenic siblings, but insulin and glucagon levels were not significantly different between the two groups. Glucose disposal following an oral glucose load was markedly enhanced in the transgenic animals, and plasma lactate and β-OH-butyrate levels were elevated in both fed and fasted transgenic mice. These data strongly support the hypothesis that glucose transport plays a key role in whole body glucose homeostasis. They also demonstrate that the level of a glucose transporter in skeletal muscle can significantly influence the blood glucose set point and alter the levels of other fuel metabolites in the blood.

Original languageEnglish
Pages (from-to)18442-18445
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number25
StatePublished - Jan 1 1993

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    Marshall, B. A., Ren, J. M., Johnson, D. W., Gibbs, E. M., Lillquist, J. S., Soeller, W. C., Holloszy, J. O., & Mueckler, M. (1993). Germline manipulation of glucose homeostasis via alteration of glucose transporter levels in skeletal muscle. Journal of Biological Chemistry, 268(25), 18442-18445.