| GLP-1 treatment reduces endogenous insulin resistance via activation of central GLP-1 receptors in mice fed a high-fat diet. | |
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MedLine Citation:
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PMID: 20530733 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucagon-like peptide-1 (GLP-1) improves insulin sensitivity in humans and rodents. It is currently unknown to what extent the (metabolic) effects of GLP-1 treatment are mediated by central GLP-1 receptors. We studied the impact of central GLP-1 receptor (GLP-1R) antagonism on the metabolic effects of peripheral GLP-1 administration in mice. High-fat-fed insulin-resistant C57Bl/6 mice were treated with continuous subcutaneous infusion of GLP-1 or saline (PBS) for 2 wk, whereas the GLP-1R antagonist exendin-9 (EX-9) and cerebrospinal fluid (CSF) were simultaneously infused in the left lateral cerebral ventricle (icv). Glucose and glycerol turnover were determined during a hyperinsulinemic euglycemic clamp. VLDL-triglyceride (VLDL-TG) production was determined in hyperinsulinemic conditions. Our data show that the rate of glucose infusion necessary to maintain euglycemia was significantly increased by GLP-1. Simultaneous icv infusion of EX-9 diminished this effect by 62%. The capacities of insulin to stimulate glucose disposal and inhibit glucose production were reinforced by GLP-1. Simultaneous icv infusion of EX-9 significantly diminished the latter effect. Central GLP-1R antagonism alone did not affect glucose metabolism. Also, GLP-1 treatment reinforced the inhibitory action of insulin on VLDL-TG production. In conclusion, peripheral administration of GLP-1 reinforces the ability of insulin to suppress endogenous glucose and VLDL-TG production (but not lipolysis) and boosts its capacity to stimulate glucose disposal in high-fat-fed C57Bl/6 mice. Activation of central GLP-1Rs contributes substantially to the inhibition of endogenous glucose production by GLP-1 treatment in this animal model. |
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Authors:
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Edwin T Parlevliet; Judith E de Leeuw van Weenen; Johannes A Romijn; Hanno Pijl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-08 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 299 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-09 Completed Date: 2010-07-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E318-24 Citation Subset: IM |
Affiliation:
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Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Body Weight / drug effects, physiology Cerebral Ventricle Neoplasms Dietary Fats / pharmacology* Fatty Acids, Nonesterified / blood Glucagon-Like Peptide 1 / pharmacology* Glucose / metabolism Glucose Clamp Technique Hyperinsulinism / metabolism Insulin / blood Insulin Resistance / physiology* Lipoproteins, VLDL / biosynthesis Male Mice Mice, Inbred C57BL Receptors, Glucagon / antagonists & inhibitors, drug effects* Triglycerides / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Dietary Fats; 0/Fatty Acids, Nonesterified; 0/Lipoproteins, VLDL; 0/Receptors, Glucagon; 0/Triglycerides; 0/glucagon-like peptide receptor; 11061-68-0/Insulin; 50-99-7/Glucose; 89750-14-1/Glucagon-Like Peptide 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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