TY - JOUR
T1 - Amelioration of insulin resistance but not hyperinsulinemia in obese mice overexpressing GLUT4 selectively in skeletal muscle
AU - Tsao, Tsu Shuen
AU - Katz, Ellen B.
AU - Pommer, David
AU - Charron, Maureen J.
N1 - Funding Information:
From the Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY SubmittedApri114, 1999; acceptedAugust 27, 1999. Supported by grants from the National Institutes of Health ([NIH] DK47425 and HL58119), American Heart Association, American Diabetes Association, and Albert Einstein College of Medicine Cancer Center (5P30CA13330), and in part by an Irma T. Hirschl Career Scientist Award (M.J.C.) and NIH grants (5T32GM07491 and 5T32HL07675 to Z-S.Z). Address reprint requests tO Maureen J. Charron, PhD, Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY10461. Copyright © 2000 by W.B. Saunders Company 0026-0495/00/4903-0011510.00/0
PY - 2000
Y1 - 2000
N2 - The effects of gold-thioglucose (GTG) treatment were examined in mice overexpressing GLUT4 selectively in skeletal muscle (MLC-GLUT4 mice) and in age-matched controls. Groups of MLC-GLUT4 and control mice were injected with GTG or saline at 5 weeks of age. At 12 weeks following the injections, GTG- treated control mice exhibited a 35% increase in body weight versus saline- treated controls. Similarly, a 30% increase in body weight was observed in GTG-treated MLC-GLUT4 mice compared with saline-treated MLC-GLUT4 mice 12 weeks after the injections. In saline-treated lean MLC-GLUT4 and control mice, intraperitoneal injection of insulin decreased blood glucose in 1 hour by 63% and 38%, respectively. Insulin also decreased blood glucose by 40% in GTG-treated obese MLC-GLUT4 mice after 1 hour. However, insulin did not reduce blood glucose levels in GTG-treated obese control mice. The ability of insulin to clear blood glucose in GTG-treated obese MLC-GLUT4 mice is associated with increased skeletal muscle GLUT4 content and white adipose tissue (WAT) GLUT4 content as compared with GTG-treated obese controls. However, fasting blood glucose levels in GTG-treated obese MLC-GLUT4 and control mice were elevated by approximately 30% compared with saline-treated groups. Lastly, although GTG-treated obese MLC-GLUT4 mice exhibited improved glucose clearance in response to insulin, they nevertheless remained as hyperinsulinemic as GTG-treated obese control mice. These results suggest that genetic overexpression of GLUT4 in skeletal muscle may ameliorate the development of insulin resistance associated with obesity but cannot restore normal glucose and insulin levels. (C) 2000 by W.B. Saunders Company.
AB - The effects of gold-thioglucose (GTG) treatment were examined in mice overexpressing GLUT4 selectively in skeletal muscle (MLC-GLUT4 mice) and in age-matched controls. Groups of MLC-GLUT4 and control mice were injected with GTG or saline at 5 weeks of age. At 12 weeks following the injections, GTG- treated control mice exhibited a 35% increase in body weight versus saline- treated controls. Similarly, a 30% increase in body weight was observed in GTG-treated MLC-GLUT4 mice compared with saline-treated MLC-GLUT4 mice 12 weeks after the injections. In saline-treated lean MLC-GLUT4 and control mice, intraperitoneal injection of insulin decreased blood glucose in 1 hour by 63% and 38%, respectively. Insulin also decreased blood glucose by 40% in GTG-treated obese MLC-GLUT4 mice after 1 hour. However, insulin did not reduce blood glucose levels in GTG-treated obese control mice. The ability of insulin to clear blood glucose in GTG-treated obese MLC-GLUT4 mice is associated with increased skeletal muscle GLUT4 content and white adipose tissue (WAT) GLUT4 content as compared with GTG-treated obese controls. However, fasting blood glucose levels in GTG-treated obese MLC-GLUT4 and control mice were elevated by approximately 30% compared with saline-treated groups. Lastly, although GTG-treated obese MLC-GLUT4 mice exhibited improved glucose clearance in response to insulin, they nevertheless remained as hyperinsulinemic as GTG-treated obese control mice. These results suggest that genetic overexpression of GLUT4 in skeletal muscle may ameliorate the development of insulin resistance associated with obesity but cannot restore normal glucose and insulin levels. (C) 2000 by W.B. Saunders Company.
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U2 - 10.1016/S0026-0495(00)90220-8
DO - 10.1016/S0026-0495(00)90220-8
M3 - Article
C2 - 10726912
AN - SCOPUS:0034018375
SN - 0026-0495
VL - 49
SP - 340
EP - 346
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 3
ER -