Document Detail

Peripheral but not hepatic insulin resistance in mice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene.
MedLine Citation:
PMID:  9312184     Owner:  NLM     Status:  MEDLINE    
Glucose transporter type 4 (GLUT4) is insulin responsive and is expressed in striated muscle and adipose tissue. To investigate the impact of a partial deficiency in the level of GLUT4 on in vivo insulin action, we examined glucose disposal and hepatic glucose production (HGP) during hyperinsulinemic clamp studies in 4-5-mo-old conscious mice with one disrupted GLUT4 allele [GLUT4 (+/-)], compared with wild-type control mice [WT (+/+)]. GLUT4 (+/-) mice were studied before the onset of hyperglycemia and had normal plasma glucose levels and a 50% increase in the fasting (6 h) plasma insulin concentrations. GLUT4 protein in muscle was approximately 45% less in GLUT4 (+/-) than in WT (+/+). Euglycemic hyperinsulinemic clamp studies were performed in combination with [3-3H]glucose to measure the rate of appearance of glucose and HGP, with [U-14C]-2-deoxyglucose to estimate muscle glucose transport in vivo, and with [U-14C]lactate to assess hepatic glucose fluxes. During the clamp studies, the rates of glucose infusion, glucose disappearance, glycolysis, glycogen synthesis, and muscle glucose uptake were approximately 55% decreased in GLUT4 (+/-), compared with WT (+/+) mice. The decreased rate of in vivo glycogen synthesis was due to decreased stimulation of glucose transport since insulin's activation of muscle glycogen synthase was similar in GLUT4 (+/-) and in WT (+/+) mice. By contrast, the ability of hyperinsulinemia to inhibit HGP was unaffected in GLUT4 (+/-). The normal regulation of hepatic glucose metabolism in GLUT4 (+/-) mice was further supported by the similar intrahepatic distribution of liver glucose fluxes through glucose cycling, gluconeogenesis, and glycogenolysis. We conclude that the disruption of one allele of the GLUT4 gene leads to severe peripheral but not hepatic insulin resistance. Thus, varying levels of GLUT4 protein in striated muscle and adipose tissue can markedly alter whole body glucose disposal. These differences most likely account for the interindividual variations in peripheral insulin action.
L Rossetti; A E Stenbit; W Chen; M Hu; N Barzilai; E B Katz; M J Charron
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  100     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-10-29     Completed Date:  1997-10-29     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1831-9     Citation Subset:  AIM; IM    
Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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MeSH Terms
Adipose Tissue / metabolism
Biological Transport
Blood Glucose / metabolism*
Glucose Clamp Technique
Glucose Transporter Type 4
Insulin / blood,  pharmacology*
Insulin Resistance / genetics*
Liver / metabolism
Mice, Mutant Strains
Monosaccharide Transport Proteins / genetics*
Muscle Proteins*
Muscle, Skeletal / metabolism
Tissue Distribution
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Glucose Transporter Type 4; 0/Monosaccharide Transport Proteins; 0/Muscle Proteins; 0/Slc2a4 protein, mouse; 11061-68-0/Insulin

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