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Expression of human GLUT4 in mice results in increased insulin action

Expression of human GLUT4 in mice results in increased insulin action 125 37 37 11 11 R. O. Deems J. L. Evans R. W. Deacon C. M. Honer D. T. Chu K. Bürki W. S. Fillers D. K. Cohen D. A. Young Diabetes Department, Preclinical Research Sandoz Research Institute, Sandoz Pharmaceuticals Corporation East Hanover New Jersey USA Preclinical Research Sandoz Pharma Ltd. Basel Switzerland Summary Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32% and 56% reduction in serum glucose and insulin and a 69% and 33% increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stimulated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14 C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin-stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating wholebody glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetologia Springer Journals

Expression of human GLUT4 in mice results in increased insulin action

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References (62)

Publisher
Springer Journals
Copyright
Copyright © 1994 by Springer-Verlag
Subject
Medicine & Public Health; Human Physiology; Internal Medicine; Metabolic Diseases
ISSN
0012-186X
eISSN
1432-0428
DOI
10.1007/BF00418373
Publisher site
See Article on Publisher Site

Abstract

125 37 37 11 11 R. O. Deems J. L. Evans R. W. Deacon C. M. Honer D. T. Chu K. Bürki W. S. Fillers D. K. Cohen D. A. Young Diabetes Department, Preclinical Research Sandoz Research Institute, Sandoz Pharmaceuticals Corporation East Hanover New Jersey USA Preclinical Research Sandoz Pharma Ltd. Basel Switzerland Summary Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32% and 56% reduction in serum glucose and insulin and a 69% and 33% increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stimulated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14 C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin-stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating wholebody glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state.

Journal

DiabetologiaSpringer Journals

Published: Nov 1, 1994

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