| Palmitic acid acutely inhibits acetylcholine- but not GLP-1-stimulated insulin secretion in mouse pancreatic islets. | |
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MedLine Citation:
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PMID: 20606076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fatty acids, acetylcholine, and GLP-1 enhance insulin secretion in a glucose-dependent manner. However, the interplay between glucose, fatty acids, and the neuroendocrine regulators of insulin secretion is not well understood. Therefore, we studied the acute effects of PA (alone or in combination with glucose, acetylcholine, or GLP-1) on isolated cultured mouse islets. Two different sets of experiments were designed. In one, a fixed concentration of 0.5 mM of PA bound to 0.15 mM BSA was used; in the other, a PA ramp from 0 to 0.5 mM was applied at a fixed albumin concentration of 0.15 mM so that the molar PA/BSA ratio changed within the physiological range. At a fixed concentration of 0.5 mM, PA markedly inhibited acetylcholine-stimulated insulin release, the rise of intracellular Ca(2+), and enhancement of cAMP production but did not influence the effects of GLP-1 on these parameters of islet cell function. 2-ADB, an IP(3) receptor inhibitor, reduced the effect of acetylcholine on insulin secretion and reversed the effect of PA on acetylcholine-stimulated insulin release. Islet perfusion for 35-40 min with 0.5 mM PA significantly reduced the calcium storage capacity of ER measured by the thapsigargin-induced Ca(2+) release. Oxygen consumption due to low but not high glucose was reduced by PA. When a PA ramp from 0 to 0.5 mM was applied in the presence of 8 mM glucose, PA at concentrations as low as 50 microM significantly augmented glucose-stimulated insulin release and markedly reduced acetylcholine's effects on hormone secretion. We thus demonstrate that PA acutely reduces the total oxygen consumption response to glucose, glucose-dependent acetylcholine stimulation of insulin release, Ca(2+), and cAMP metabolism, whereas GLP-1's actions on these parameters remain unaffected or potentiated. We speculate that acute emptying of the ER calcium by PA results in decreased glucose stimulation of respiration and acetylcholine potentiation of insulin secretion. |
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Authors:
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Nicolai M Doliba; Wei Qin; Sergei A Vinogradov; David F Wilson; Franz M Matschinsky |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-06 |
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 Sep |
Date Detail:
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Created Date: 2010-08-26 Completed Date: 2010-10-06 Revised Date: 2011-09-13 |
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: E475-85 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Biophysics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, 19104-6140, USA. nicolai@mail.med.upenn.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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antagonists & inhibitors*,
metabolism Animals Calcium / metabolism Cyclic AMP / metabolism Glucagon-Like Peptide 1 / metabolism* Insulin / secretion* Islets of Langerhans / drug effects*, physiology*, secretion Mice Mice, Inbred C57BL Oxygen Consumption / physiology Palmitic Acid / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK-19525/DK/NIDDK NIH HHS; DK-22122/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 51-84-3/Acetylcholine; 57-10-3/Palmitic Acid; 60-92-4/Cyclic AMP; 7440-70-2/Calcium; 89750-14-1/Glucagon-Like Peptide 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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