Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
Open Access
- 15 June 2000
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 105 (12), 1791-1797
- https://doi.org/10.1172/jci8305
Abstract
Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are normoglycemic but have increased fat mass. To identify the potential mechanism for this important association, we examined insulin action in specific tissues of MIRKO and control mice under hyperinsulinemic-euglycemic conditions. We found that insulin-stimulated muscle glucose transport and glycogen synthesis were decreased by about 80% in MIRKO mice, whereas insulin-stimulated fat glucose transport was increased threefold in MIRKO mice. These data demonstrate that selective insulin resistance in muscle promotes redistribution of substrates to adipose tissue thereby contributing to increased adiposity and development of the prediabetic syndrome.Keywords
This publication has 28 references indexed in Scilit:
- Molecular mechanisms of insulin action in normal and insulin-resistant statesExperimental and Clinical Endocrinology & Diabetes, 1999
- Early neonatal death in mice homozygous for a null allele of the insulin receptor geneNature Genetics, 1996
- Fasting does not impair insulin-stimulated glucose uptake but alters intracellular glucose metabolism in conscious ratsDiabetes, 1993
- Glucose Transport and NIDDMDiabetes Care, 1992
- Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles : a clue for increased fat depot and insulin resistanceEndocrinology, 1990
- Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake. A dose-response euglycemic clamp study in normal and diabetic rats.JCI Insight, 1990
- Where All the Glucose Doesn't Go in Non-Insulin-Dependent Diabetes MellitusNew England Journal of Medicine, 1990
- Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by13C Nuclear Magnetic Resonance SpectroscopyNew England Journal of Medicine, 1990
- Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.JCI Insight, 1988
- Muscle Glucose Metabolism following Exercise in the RatJCI Insight, 1982