| Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion. | |
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MedLine Citation:
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PMID: 19389712 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reduced lipolysis in hormone-sensitive lipase-deficient mice is associated with impaired glucose-stimulated insulin secretion (GSIS), suggesting that endogenous beta-cell lipid stores provide signaling molecules for insulin release. Measurements of lipolysis and triglyceride (TG) lipase activity in islets from HSL(-/-) mice indicated the presence of other TG lipase(s) in the beta-cell. Using real time-quantitative PCR, adipose triglyceride lipase (ATGL) was found to be the most abundant TG lipase in rat islets and INS832/13 cells. To assess its role in insulin secretion, ATGL expression was decreased in INS832/13 cells (ATGL-knockdown (KD)) by small hairpin RNA. ATGL-KD increased the esterification of free fatty acid (FFA) into TG. ATGL-KD cells showed decreased glucose- or Gln + Leu-induced insulin release, as well as reduced response to KCl or palmitate at high, but not low, glucose. The K(ATP)-independent/amplification pathway of GSIS was considerably reduced in ATGL-KD cells. ATGL(-/-) mice were hypoinsulinemic and hypoglycemic and showed decreased plasma TG and FFAs. A hyperglycemic clamp revealed increased insulin sensitivity and decreased GSIS and arginine-induced insulin secretion in ATGL(-/-) mice. Accordingly, isolated islets from ATGL(-/-) mice showed reduced insulin secretion in response to glucose, glucose + palmitate, and KCl. Islet TG content and FFA esterification into TG were increased by 2-fold in ATGL(-/-) islets, but glucose usage and oxidation were unaltered. The results demonstrate the importance of ATGL and intracellular lipid signaling for fuel- and non-fuel-induced insulin secretion. |
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Authors:
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Marie-Line Peyot; Claudiane Guay; Martin G Latour; Julien Lamontagne; Roxane Lussier; Marco Pineda; Neil B Ruderman; Guenter Haemmerle; Rudolf Zechner; Erik Joly; S R Murthy Madiraju; Vincent Poitout; Marc Prentki |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-04-22 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-15 Completed Date: 2009-10-20 Revised Date: 2010-09-24 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 16848-59 Citation Subset: IM |
Affiliation:
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Molecular Nutrition Unit and Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec H1W4A4, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Carboxylic Ester Hydrolases / deficiency, genetics, metabolism* Cell Line Fasting / metabolism Fatty Acids, Nonesterified / metabolism Glucose / pharmacology Glucose Clamp Technique Insulin / secretion* Islets of Langerhans / drug effects, metabolism, secretion Lipase / antagonists & inhibitors, genetics, metabolism Lipolysis Male Mice Mice, Knockout RNA, Small Interfering / genetics Rats Signal Transduction Triglycerides / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 0/RNA, Small Interfering; 0/Triglycerides; 11061-68-0/Insulin; 50-99-7/Glucose; EC 3.1.1.-/Carboxylic Ester Hydrolases; EC 3.1.1.1/desnutrin protein, mouse; EC 3.1.1.3/Lipase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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