Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle

Tsu Shuen Tsao, Rémy Burcelin, Ellen B. Katz, Lily Huang, Maureen J. Charron

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Dysregulation of GLUT4, the insulin-responsive glucose transporter, is associated with insulin resistance in skeletal muscle. Although skeletal muscle is the major target of insulin action, muscle GLUT4 has not been linked causally to whole-body insulin sensitivity and regulation of glucose homeostasis. To address this, we generated a line of transgenic mice that overexpresses GLUT4 in skeletal muscle. We demonstrate that restricted overexpression of GLUT4 in fast-twitch skeletal muscles of myosin light chain (MLC)-GLUT4 transgenic mice induces a 2.5-fold increase in insulin-stimulated 2-deoxyglucose uptake in transgene-overexpressing cells. Consequently, glycogen content is increased in the fast-twitch skeletal muscles under insulin action (5.75 ± 1.02 vs. 3.24 ± 0.26 mg/g). This indicates that insulin-stimulated glucose transport is partly rate-limiting for glycogen synthesis. At the whole-body level, insulin-stimulated glucose turnover is increased 2.5-fold in unconscious MLC-GLUT4 mice. Plasma glucose and insulin levels in MLC-GLUT4 mice are altered as a result of increased insulin action. In 2- to 3-month-old MLC-GLUT4 mice, fasting insulin levels are decreased (0.43 ± 0.05 vs. 0.74 ± 0.10 μg/l), whereas normal fasting glycemia is maintained. Conversely, 7- to 9-month-old MLC-GLUT4 mice exhibit decreased fasting glycemia (5.75 ± 0.73 vs. 8.11 ± 0.57 mmol/l) with normal insulin levels. Fasting plasma lactate levels are elevated in both age groups (50- 100%). Additionally, lipid metabolism is affected by skeletal muscle GLUT4 overexpression. This is indicated by changes in plasma free fatty acid and β-hydroxybutyrate levels. These studies underscore the importance of GLUT4 in the regulation of glucose homeostasis and its interaction with lipid metabolism.

Original languageEnglish (US)
Pages (from-to)28-36
Number of pages9
JournalDiabetes
Volume45
Issue number1
StatePublished - Jan 1996

Fingerprint

Insulin
Myosin Light Chains
Muscles
Skeletal Muscle
Fasting
Glucose
Glycogen
Lipid Metabolism
Transgenic Mice
Insulin Resistance
Homeostasis
Skeletal Muscle Myosins
Glucose Transporter Type 4
Hydroxybutyrates
Deoxyglucose
Transgenes
Nonesterified Fatty Acids
Lactic Acid
Age Groups

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tsao, T. S., Burcelin, R., Katz, E. B., Huang, L., & Charron, M. J. (1996). Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle. Diabetes, 45(1), 28-36.

Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle. / Tsao, Tsu Shuen; Burcelin, Rémy; Katz, Ellen B.; Huang, Lily; Charron, Maureen J.

In: Diabetes, Vol. 45, No. 1, 01.1996, p. 28-36.

Research output: Contribution to journalArticle

Tsao, TS, Burcelin, R, Katz, EB, Huang, L & Charron, MJ 1996, 'Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle', Diabetes, vol. 45, no. 1, pp. 28-36.
Tsao, Tsu Shuen ; Burcelin, Rémy ; Katz, Ellen B. ; Huang, Lily ; Charron, Maureen J. / Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle. In: Diabetes. 1996 ; Vol. 45, No. 1. pp. 28-36.
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