HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 30, 20958-20973, July 28, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/30/20958    most recent M600075200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bao, S. Articles by Turk, J. Search for Related Content PubMed PubMed Citation Articles by Bao, S. Articles by Turk, J. Social Bookmarking                      What's this?

Insulin Secretory Responses and Phospholipid Composition of Pancreatic Islets from Mice That Do Not Express Group VIA Phospholipase A₂ and Effects of Metabolic Stress on Glucose Homeostasis^*

From the Mass Spectrometry Facility and Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110

Studies involving pharmacologic or molecular biologic manipulation of Group VIA phospholipase A₂ (iPLA₂) activity in pancreatic islets and insulinoma cells suggest that iPLA₂ participates in insulin secretion. It has also been suggested that iPLA₂ is a housekeeping enzyme that regulates cell 2-lysophosphatidylcholine (LPC) levels and arachidonate incorporation into phosphatidylcholine (PC). We have generated iPLA₂-null mice by homologous recombination and have reported that they exhibit reduced male fertility and defective motility of spermatozoa. Here we report that pancreatic islets from iPLA₂-null mice have impaired insulin secretory responses to D-glucose and forskolin. Electrospray ionization mass spectrometric analyses indicate that the abundance of arachidonate-containing PC species of islets, brain, and other tissues from iPLA₂-null mice is virtually identical to that of wild-type mice, and no iPLA₂ mRNA was observed in any tissue from iPLA₂-null mice at any age. Despite the insulin secretory abnormalities of isolated islets, fasting and fed blood glucose concentrations of iPLA₂-null and wild-type mice are essentially identical under normal circumstances, but iPLA₂-null mice develop more severe hyperglycemia than wild-type mice after administration of multiple low doses of the -cell toxin streptozotocin, suggesting an impaired islet secretory reserve. A high fat diet also induces more severe glucose intolerance in iPLA₂-null mice than in wild-type mice, but PLA₂-null mice have greater responsiveness to exogenous insulin than do wild-type mice fed a high fat diet. These and previous findings thus indicate that iPLA₂-null mice exhibit phenotypic abnormalities in pancreatic islets in addition to testes and macrophages.

Received for publication, January 4, 2006 , and in revised form, April 17, 2006.

^* This work was supported by United States Public Health Service Grants R37-DK34388, P01-HL57278, P41-RR00954, P60-DK20579, R01-69455, and P30-DK56341. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental figures.

¹ To whom correspondence should be addressed: Washington University School of Medicine, Campus Box 8127, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-8190; Fax: 314-362-7641; E-mail: jturk{at}wustl.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. E. Burke and E. A. Dennis Phospholipase A2 structure/function, mechanism, and signaling J. Lipid Res., April 1, 2009; 50(Supplement): S237 - S242. [Abstract] [Full Text] [PDF]

				P. Bougneres and A.-J. Valleron Causes of early-onset type 1 diabetes: toward data-driven environmental approaches J. Exp. Med., December 22, 2008; 205(13): 2953 - 2957. [Abstract] [Full Text] [PDF]

				S. H. Moon, C. M. Jenkins, D. J. Mancuso, J. Turk, and R. W. Gross Smooth Muscle Cell Arachidonic Acid Release, Migration, and Proliferation Are Markedly Attenuated in Mice Null for Calcium-independent Phospholipase A2{beta} J. Biol. Chem., December 5, 2008; 283(49): 33975 - 33987. [Abstract] [Full Text] [PDF]

				S. Ramanadham, K. E. Yarasheski, M. J. Silva, M. Wohltmann, D. V. Novack, B. Christiansen, X. Tu, S. Zhang, X. Lei, and J. Turk Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2{beta})-Null Mice Am. J. Pathol., April 1, 2008; 172(4): 868 - 881. [Abstract] [Full Text] [PDF]

				S. Bao, D. A. Jacobson, M. Wohltmann, A. Bohrer, W. Jin, L. H. Philipson, and J. Turk Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2{beta} in pancreatic {beta}-cells and in iPLA2{beta}-null mice Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E217 - E229. [Abstract] [Full Text] [PDF]

				V. Poitout Phospholipid hydrolysis and insulin secretion: a step toward solving the Rubik's cube Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E214 - E216. [Full Text] [PDF]

				I. Malik, J. Turk, D. J. Mancuso, L. Montier, M. Wohltmann, D. F. Wozniak, R. E. Schmidt, R. W. Gross, and P. T. Kotzbauer Disrupted Membrane Homeostasis and Accumulation of Ubiquitinated Proteins in a Mouse Model of Infantile Neuroaxonal Dystrophy Caused by PLA2G6 Mutations Am. J. Pathol., February 1, 2008; 172(2): 406 - 416. [Abstract] [Full Text] [PDF]

				D. M. Nikolic, M. C. Gong, J. Turk, and S. R. Post Class A Scavenger Receptor-mediated Macrophage Adhesion Requires Coupling of Calcium-independent Phospholipase A2 and 12/15-Lipoxygenase to Rac and Cdc42 Activation J. Biol. Chem., November 16, 2007; 282(46): 33405 - 33411. [Abstract] [Full Text] [PDF]

				S. Bao, Y. Li, X. Lei, M. Wohltmann, W. Jin, A. Bohrer, C. F. Semenkovich, S. Ramanadham, I. Tabas, and J. Turk Attenuated Free Cholesterol Loading-induced Apoptosis but Preserved Phospholipid Composition of Peritoneal Macrophages from Mice That Do Not Express Group VIA Phospholipase A2 J. Biol. Chem., September 14, 2007; 282(37): 27100 - 27114. [Abstract] [Full Text] [PDF]

				Z. Xie, M. C. Gong, W. Su, J. Turk, and Z. Guo Group VIA Phospholipase A2 (iPLA2beta) Participates in Angiotensin II-induced Transcriptional Up-regulation of Regulator of G-protein Signaling-2 in Vascular Smooth Muscle Cells J. Biol. Chem., August 31, 2007; 282(35): 25278 - 25289. [Abstract] [Full Text] [PDF]

				H. Kuwata, C. Fujimoto, E. Yoda, S. Shimbara, Y. Nakatani, S. Hara, M. Murakami, and I. Kudo A Novel Role of Group VIB Calcium-independent Phospholipase A2 (iPLA2{gamma}) in the Inducible Expression of Group IIA Secretory PLA2 in Rat Fibroblastic Cells J. Biol. Chem., July 13, 2007; 282(28): 20124 - 20132. [Abstract] [Full Text] [PDF]

				D. A. Jacobson, C. R. Weber, S. Bao, J. Turk, and L. H. Philipson Modulation of the Pancreatic Islet beta-Cell-delayed Rectifier Potassium Channel Kv2.1 by the Polyunsaturated Fatty Acid Arachidonate J. Biol. Chem., March 9, 2007; 282(10): 7442 - 7449. [Abstract] [Full Text] [PDF]

				M. Ohtsuki, Y. Taketomi, S. Arata, S. Masuda, Y. Ishikawa, T. Ishii, Y. Takanezawa, J. Aoki, H. Arai, K. Yamamoto, et al. Transgenic Expression of Group V, but Not Group X, Secreted Phospholipase A2 in Mice Leads to Neonatal Lethality because of Lung Dysfunction J. Biol. Chem., November 24, 2006; 281(47): 36420 - 36433. [Abstract] [Full Text] [PDF]

				G. T. Wijewickrama, A. Albanese, Y. J. Kim, Y. S. Oh, P. S. Murray, R. Takayanagi, T. Tobe, S. Masuda, M. Murakami, I. Kudo, et al. Unique Membrane Interaction Mode of Group IIF Phospholipase A2 J. Biol. Chem., October 27, 2006; 281(43): 32741 - 32754. [Abstract] [Full Text] [PDF]