| S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats. | |
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MedLine Citation:
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PMID: 20599729 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ( approximately 18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15day, 10nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPARgamma) agonist pioglitazone significantly (P<0.001) restored S961 induced hyperglycemia (196.73+/-16.32 vs. 126.37+/-27.07 mg/dl) and glucose intolerance (approximately 78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism. |
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Authors:
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Ajit Vikram; Gopabandhu Jena |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-19 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 398 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-08-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 260-5 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Glucose / metabolism Glucose Tolerance Test Hyperglycemia / chemically induced, metabolism Hyperinsulinism / chemically induced*, metabolism Hypoglycemic Agents / pharmacology Insulin Resistance* Liver Glycogen / metabolism Peptides / pharmacology* Rats Rats, Sprague-Dawley Receptor, Insulin / antagonists & inhibitors* Thiazolidinediones / pharmacology Triglycerides / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Hypoglycemic Agents; 0/Liver Glycogen; 0/Peptides; 0/S961 peptide; 0/Thiazolidinediones; 0/Triglycerides; 111025-46-8/pioglitazone; 50-99-7/Glucose; EC 2.7.10.1/Receptor, Insulin |
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