title: Redox Signal-mediated Enhancement of the Temperature Sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) Elevates Glucose-induced Insulin Secretion from Pancreatic Islets.
abstract: Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive Ca(2+)-permeable cation channel expressed by pancreatic β cells where channel function is constantly affected by body temperature. We focused on the physiological functions of redox signal-mediated TRPM2 activity at body temperature. H2O2, an important molecule in redox signaling, reduced the temperature threshold for TRPM2 activation in pancreatic β cells of WT mice but not in TRPM2KO cells. TRPM2-mediated [Ca(2+)]i increases were likely caused by Ca(2+) influx through the plasma membrane because the responses were abolished in the absence of extracellular Ca(2+). In addition, TRPM2 activation downstream from the redox signal plus glucose stimulation enhanced glucose-induced insulin secretion. H2O2 application at 37 °C induced [Ca(2+)]i increases not only in WT but also in TRPM2KO β cells. This was likely due to the effect of H2O2 on KATP channel activity. However, the N-acetylcysteine-sensitive fraction of insulin secretion by WT islets was increased by temperature elevation, and this temperature-dependent enhancement was diminished significantly in TRPM2KO islets. These data suggest that endogenous redox signals in pancreatic β cells elevate insulin secretion via TRPM2 sensitization and activity at body temperature. The results in this study could provide new therapeutic approaches for the regulation of diabetic conditions by focusing on the physiological function of TRPM2 and redox signals.
authors.affiliation: From the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan and.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kashio
authors.affiliation: From the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan and the Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8585, Japan tominaga@nips.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000737:chemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000378:metabolism*; D013696:Temperature
chemical_list: D000975:Antioxidants; D005456:Fluorescent Dyes; D007328:Insulin; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; D006861:Hydrogen Peroxide; D005947:Glucose; D002118:Calcium
keywords: calcium channel; glucose; insulin; ion channel; redox signaling
references.citation: Diabetes. 2011 Jan;60(1):119-26
references.pmid: 20921208
references.citation: Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327-31
references.pmid: 28524
references.citation: Br J Pharmacol. 2012 Feb;165(4):787-801
references.pmid: 21797839
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6745-50
references.pmid: 22493272
references.citation: Handb Exp Pharmacol. 2014;222:403-26
references.pmid: 24756715
references.citation: Biochim Biophys Acta. 2006 Dec;1764(12):1823-41
references.pmid: 17070740
references.citation: Transplantation. 1986 Dec;42(6):689-91
references.pmid: 3024372
references.citation: Handb Exp Pharmacol. 2014;223:729-41
references.pmid: 24961967
references.citation: Diabetes. 2014 Oct;63(10):3394-403
references.pmid: 24824430
references.citation: Cell Calcium. 2014 Nov;56(5):332-9
references.pmid: 25084624
references.citation: J Endocrinol. 1990 Apr;125(1):45-51
references.pmid: 2187049
references.citation: FEBS Lett. 1993 Mar 15;319(1-2):128-32
references.pmid: 8454044
references.citation: Free Radic Biol Med. 1996;20(3):463-6
references.pmid: 8720919
references.citation: J Clin Invest. 2009 Nov;119(11):3246-56
references.pmid: 19805912
references.citation: Pflugers Arch. 2009 Oct;458(6):1093-102
references.pmid: 19669158
references.citation: EMBO J. 2006 May 3;25(9):1804-15
references.pmid: 16601673
references.citation: ACS Chem Biol. 2010 Jan 15;5(1):47-62
references.pmid: 19957967
references.citation: Adv Exp Med Biol. 2010;654:193-216
references.pmid: 20217499
references.citation: Adv Exp Med Biol. 2010;654:235-59
references.pmid: 20217501
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5208-13
references.pmid: 20194741
references.citation: J Physiol. 2010 Apr 15;588(Pt 8):1227-40
references.pmid: 20194125
references.citation: Annu Rev Biochem. 2007;76:387-417
references.pmid: 17579562
references.citation: Diabetes. 2007 Jul;56(7):1783-91
references.pmid: 17400930
references.citation: J Physiol. 2007 Aug 15;583(Pt 1):9-24
references.pmid: 17584843
references.citation: Nat Med. 2008 Jul;14(7):738-47
references.pmid: 18542050
references.citation: J Neurosci. 2008 Dec 17;28(51):13727-37
references.pmid: 19091963
references.citation: Endocrinology. 2009 May;150(5):2197-201
references.pmid: 19147679
references.citation: Sci Signal. 2009;2(71):ra23
references.pmid: 19454650
references.citation: Science. 2001 Aug 17;293(5533):1327-30
references.pmid: 11509734
references.citation: Neuron. 2011 May 12;70(3):482-94
references.pmid: 21555074