Insulin signaling and glucose transport in insulin resistant skeletal muscle

Special reference to GLUT4 transgenic and GLUT4 knockout mice

D. Galuska, J. Ryder, Y. Kawano, Maureen J. Charron, J. R. Zierath

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Glucose homeostasis is impaired in patients with non-insulin dependent diabetes mellitus (NIDDM) and this defect is due in part, to defects in glucose transport in skeletal muscle. Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane. Recently, potential targets for impaired traffic/translocation of GLUT4 have been reported to include defective phosphorylation of IRS-1 and reduced PI-3 kinase activity. In addition to insulin signaling defects, impaired glucose transport may result from a defect(s) in the activation or functional capacity of GLUT4. Because GLUT4 is dysregulated in skeletal muscle from NIDDM patients, it is an attractive target for gene therapy. Overexpression of GLUT4 in muscle results in increased glucose uptake and metabolism, and protects against the development of insulin resistance in transgenic mice. Genetic ablation of GLUT4 results in impaired insulin tolerance and defects in glucose metabolism in skeletal muscle. Because impaired muscle glucose transport leads to reduced whole body glucose uptake and hyperglycemia, understanding the molecular regulation of glucose transport in skeletal muscle is necessary to develop effective strategies to prevent or reduce the incidence of NIDDM.

Original languageEnglish (US)
Pages (from-to)73-85
Number of pages13
JournalAdvances in Experimental Medicine and Biology
Volume441
StatePublished - 1998
Externally publishedYes

Fingerprint

Knockout Mice
Muscle
Skeletal Muscle
Insulin
Glucose
Medical problems
Type 2 Diabetes Mellitus
Defects
Metabolism
Muscles
Gene therapy
Signal transduction
Phosphorylation
Cell membranes
Ablation
Phosphatidylinositol 3-Kinases
Hyperglycemia
Genetic Therapy
Transgenic Mice
Insulin Resistance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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abstract = "Glucose homeostasis is impaired in patients with non-insulin dependent diabetes mellitus (NIDDM) and this defect is due in part, to defects in glucose transport in skeletal muscle. Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane. Recently, potential targets for impaired traffic/translocation of GLUT4 have been reported to include defective phosphorylation of IRS-1 and reduced PI-3 kinase activity. In addition to insulin signaling defects, impaired glucose transport may result from a defect(s) in the activation or functional capacity of GLUT4. Because GLUT4 is dysregulated in skeletal muscle from NIDDM patients, it is an attractive target for gene therapy. Overexpression of GLUT4 in muscle results in increased glucose uptake and metabolism, and protects against the development of insulin resistance in transgenic mice. Genetic ablation of GLUT4 results in impaired insulin tolerance and defects in glucose metabolism in skeletal muscle. Because impaired muscle glucose transport leads to reduced whole body glucose uptake and hyperglycemia, understanding the molecular regulation of glucose transport in skeletal muscle is necessary to develop effective strategies to prevent or reduce the incidence of NIDDM.",
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AU - Ryder, J.

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AU - Charron, Maureen J.

AU - Zierath, J. R.

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AB - Glucose homeostasis is impaired in patients with non-insulin dependent diabetes mellitus (NIDDM) and this defect is due in part, to defects in glucose transport in skeletal muscle. Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane. Recently, potential targets for impaired traffic/translocation of GLUT4 have been reported to include defective phosphorylation of IRS-1 and reduced PI-3 kinase activity. In addition to insulin signaling defects, impaired glucose transport may result from a defect(s) in the activation or functional capacity of GLUT4. Because GLUT4 is dysregulated in skeletal muscle from NIDDM patients, it is an attractive target for gene therapy. Overexpression of GLUT4 in muscle results in increased glucose uptake and metabolism, and protects against the development of insulin resistance in transgenic mice. Genetic ablation of GLUT4 results in impaired insulin tolerance and defects in glucose metabolism in skeletal muscle. Because impaired muscle glucose transport leads to reduced whole body glucose uptake and hyperglycemia, understanding the molecular regulation of glucose transport in skeletal muscle is necessary to develop effective strategies to prevent or reduce the incidence of NIDDM.

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