Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells.
| Title: | Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. |
|---|---|
| Authors: | Dominguez V; From the Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Centre for Diabetes, London E1 2AT, United Kingdom.; Raimondi C; Somanath S; Bugliani M; Loder MK; Edling CE; Divecha N; da Silva-Xavier G; Marselli L; Persaud SJ; Turner MD; Rutter GA; Marchetti P; Falasca M; Maffucci T |
| Source: | The Journal of biological chemistry [J Biol Chem] 2011 Feb 11; Vol. 286 (6), pp. 4216-25. Date of Electronic Publication: 2010 Dec 02. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology; Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| MeSH Terms: | Down-Regulation* ; Exocytosis* ; Gene Expression Regulation, Enzymologic*; Diabetes Mellitus, Type 2/*metabolism ; Insulin/*metabolism ; Insulin-Secreting Cells/*metabolism ; Phosphatidylinositol 3-Kinases/*biosynthesis ; Secretory Vesicles/*metabolism; Diabetes Mellitus, Type 2/genetics ; Insulin/genetics ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Synaptosomal-Associated Protein 25/genetics ; Synaptosomal-Associated Protein 25/metabolism ; Animals ; Cell Line, Tumor ; Humans ; Insulin Secretion ; Rats |
| Abstract: | Phosphoinositide 3-kinases (PI3Ks) are critical regulators of pancreatic β cell mass and survival, whereas their involvement in insulin secretion is more controversial. Furthermore, of the different PI3Ks, the class II isoforms were detected in β cells, although their role is still not well understood. Here we show that down-regulation of the class II PI3K isoform PI3K-C2α specifically impairs insulin granule exocytosis in rat insulinoma cells without affecting insulin content, the number of insulin granules at the plasma membrane, or the expression levels of key proteins involved in insulin secretion. Proteolysis of synaptosomal-associated protein of 25 kDa, a process involved in insulin granule exocytosis, is impaired in cells lacking PI3K-C2α. Finally, our data suggest that the mRNA for PI3K-C2α may be down-regulated in islets of Langerhans from type 2 diabetic compared with non-diabetic individuals. Our results reveal a critical role for PI3K-C2α in β cells and suggest that down-regulation of PI3K-C2α may be a feature of type 2 diabetes. |
| References: | Islets. 2009 Sep-Oct;1(2):106-10. (PMID: 21099257); Diabetologia. 2007 Jun;50(6):1239-42. (PMID: 17440705); Cell. 1999 Feb 5;96(3):329-39. (PMID: 10025399); Front Horm Res. 2008;36:118-134. (PMID: 18230899); Diabetes Obes Metab. 2008 Nov;10 Suppl 4:32-42. (PMID: 18834431); FASEB J. 2008 Jan;22(1):194-206. (PMID: 17709608); J Endocrinol. 2000 Jul;166(1):111-20. (PMID: 10856889); J Endocrinol. 2002 Aug;174(2):247-58. (PMID: 12176663); J Cell Sci. 2004 Jul 1;117(Pt 15):3119-27. (PMID: 15190121); Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16191-6. (PMID: 19805279); Curr Biol. 2000 Oct 19;10(20):1307-10. (PMID: 11069115); J Biol Chem. 2007 Sep 21;282(38):28226-36. (PMID: 17644513); Mol Genet Metab. 2005 May;85(1):54-60. (PMID: 15862281); Diabetes. 2009 Apr;58(4):894-905. (PMID: 19168596); Mol Biol Cell. 2008 Dec;19(12):5593-603. (PMID: 18843041); Diabetes. 2006 Oct;55(10):2835-42. (PMID: 17003350); Biochem Biophys Res Commun. 2008 Jan 18;365(3):466-71. (PMID: 17991425); J Biol Chem. 2000 May 12;275(19):14025-30. (PMID: 10799475); Diabetologia. 2004 Nov;47(11):1861-72. (PMID: 15551048); Biochem Soc Trans. 2007 Apr;35(Pt 2):211-4. (PMID: 17371240); Diabetes. 2005 Mar;54(3):727-35. (PMID: 15734849); Regul Pept. 2008 Feb 7;146(1-3):4-11. (PMID: 17889380); Biochim Biophys Acta. 2009 Dec;1793(12):1795-803. (PMID: 19852987); Mol Endocrinol. 2007 Nov;21(11):2775-84. (PMID: 17652185); Science. 2002 May 31;296(5573):1655-7. (PMID: 12040186); EMBO J. 2003 Aug 15;22(16):4178-89. (PMID: 12912916); Mol Biol Cell. 2005 Oct;16(10):4841-51. (PMID: 16055506); Mol Aspects Med. 2001 Dec;22(6):247-84. (PMID: 11890977); Biochem J. 2004 Jan 1;377(Pt 1):149-58. (PMID: 14563207); J Cell Biol. 2005 Jun 6;169(5):789-99. (PMID: 15928202); Diabetologia. 2003 Aug;46(8):1029-45. (PMID: 12879249); Biochem J. 1997 Aug 15;326 ( Pt 1):139-47. (PMID: 9337861); Curr Biol. 2003 Apr 1;13(7):563-7. (PMID: 12676086); Diabetologia. 2007 Dec;50(12):2486-94. (PMID: 17906960); Diabetes. 2009 Sep;58(9):2070-83. (PMID: 19542200); Endocrinology. 2006 Jul;147(7):3318-25. (PMID: 16574789); Biochem Biophys Res Commun. 2009 Sep 18;387(2):310-5. (PMID: 19591801); Mol Cell. 1998 May;1(6):933-8. (PMID: 9660977); Mol Genet Metab. 2007 Aug;91(4):318-24. (PMID: 17572128); Trends Biochem Sci. 2009 Mar;34(3):115-27. (PMID: 19299143); Biochem Biophys Res Commun. 1995 Sep 5;214(1):51-9. (PMID: 7669052); Diabetes Metab Res Rev. 2007 Oct;23(7):518-27. (PMID: 17883249); Diabetes Care. 2001 Jan;24(1):89-94. (PMID: 11194248); Mol Endocrinol. 2005 Jan;19(1):213-24. (PMID: 15471947); Mol Cancer Res. 2008 Apr;6(4):614-23. (PMID: 18403640); J Cell Biol. 1981 Apr;89(1):141-5. (PMID: 7014571); Biochem J. 2003 Dec 15;376(Pt 3):625-32. (PMID: 12974673); Endocrinology. 2004 Sep;145(9):4078-83. (PMID: 15231713); J Biol Chem. 2009 Oct 2;284(40):27114-22. (PMID: 19654322); Diabetologia. 2009 May;52(5):739-51. (PMID: 19288076); Diabetes. 1995 Nov;44(11):1249-58. (PMID: 7589820); FASEB J. 2010 Jun;24(6):1824-37. (PMID: 20061534); Diabetes. 2009 Sep;58(9):2084-92. (PMID: 19549714); Diabetes. 2003 Jan;52(1):102-10. (PMID: 12502499) |
| Grant Information: | 13/0004672 United Kingdom DUK_ Diabetes UK; G0401641 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust |
| Substance Nomenclature: | 0 (Insulin); 0 (Isoenzymes); 0 (RNA, Messenger); 0 (Synaptosomal-Associated Protein 25); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (PIK3C2A protein, human) |
| Entry Date(s): | Date Created: 20101204 Date Completed: 20110324 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3039383 |
| DOI: | 10.1074/jbc.M110.200295 |
| PMID: | 21127054 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't