| Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts. | |
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MedLine Citation:
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PMID: 20130739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. The results showed that diabetes (D) decreased the tau value on the coronary endothelium and increased it on cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. On the coronary endothelium, tau values of DI and DIDp were normalized. Western blots of the insulin receptor showed upregulation in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4. |
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Authors:
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Christine M Hantouche; Khalil M Bitar; Georges M Nemer; Mounir Y Obeid; Lina N Kadi; Asdghig H Der-Boghossian; Anwar B Bikhazi |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Canadian journal of physiology and pharmacology Volume: 88 ISSN: 1205-7541 ISO Abbreviation: Can. J. Physiol. Pharmacol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-04 Completed Date: 2010-08-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372712 Medline TA: Can J Physiol Pharmacol Country: Canada |
Other Details:
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Languages: eng Pagination: 54-63 Citation Subset: IM |
Affiliation:
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Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-236, Lebanon. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Cattle Diabetes Mellitus, Experimental / drug therapy, metabolism*, physiopathology* Glucagon-Like Peptide 1 / analogs & derivatives*, physiology*, therapeutic use Insulin / administration & dosage, therapeutic use Male Peptides / administration & dosage, therapeutic use Protein Binding / drug effects Rats Rats, Sprague-Dawley Receptor, Insulin / metabolism* Venoms / administration & dosage, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Peptides; 0/Venoms; 11061-68-0/Insulin; 141732-76-5/exenatide; 89750-14-1/Glucagon-Like Peptide 1; EC 2.7.10.1/Receptor, Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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