Recent Publications from Members of the BIIC

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You are hereRecent Publications of Members of the Boston Ithaca Islet Club / Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion

Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion

By JPGRAY - Posted on 23 August 2009

Title	Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion
Publication Type	Journal Article
Year of Publication	2009
Authors	Peyot ML, Guay C, Latour MG, Lamontagne J, Lussier R, Pineda M, Ruderman NB, Haemmerle G, Zechner R, Joly E, Madiraju SR, Poitout V, Prentki M
Journal	J Biol Chem
Volume	284
Issue	25
Pagination	16848-59
Date Published	Jun 19
Publication Language	eng
ISBN Number	0021-9258 (Print)
Accession Number	19389712
Abstract	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.
Notes	Journal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States
URL	http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19389712
Citation Key	558
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