title: TRPM5 regulates glucose-stimulated insulin secretion.
abstract: Insulin secretion in beta-pancreatic cells due to glucose stimulation requires the coordinated alteration of cellular ion concentrations and a substantial membrane depolarization to enable insulin vesicle fusion with the cellular membrane. The cornerstones of this cascade are well characterized, yet current knowledge argues for the involvement of additional ion channels in this process. TRPM5 is a cation channel expressed in beta-cells and proposed to be involved in coupling intracellular Ca(2+) release to electrical activity and cellular responses. Here, we report that TRPM5 acts as an indispensable regulator of insulin secretion. In vivo glucose tolerance tests showed that Trpm5 (-/-) -mice maintain elevated blood glucose levels for over an hour compared to wild-type littermates, while insulin sensitivity is normal in Trpm5 (-/-) -mice. In pancreatic islets isolated from Trpm5 (-/-) -mice, hyperglycemia as well as arginine-induced insulin secretion was diminished. The presented results describe a major role for TRPM5 in glucose-induced insulin secretion beyond membrane depolarization. Dysfunction of the TRPM5 protein could therefore be an important factor in the etiology of some forms of type 2 diabetes, where disruption of the normal pattern of secretion is observed.
authors.affiliation: Centre for Paediatrics and Adolescent Medicine, University Medical Centre of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 63, 55131 Mainz, Germany.
authors.forename: Lili R
authors.initials: LR
authors.lastname: Brixel
authors.forename: Mahealani K
authors.initials: MK
authors.lastname: Monteilh-Zoller
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Ingenbrandt
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.forename: Reinhold
authors.initials: R
authors.lastname: Penner
authors.forename: Thorsten
authors.initials: T
authors.lastname: Enklaar
authors.forename: Bernhard U
authors.initials: BU
authors.lastname: Zabel
authors.forename: Dirk
authors.initials: D
authors.lastname: Prawitt
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D050053:TRPM Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D001786:Blood Glucose; D007328:Insulin; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; D001120:Arginine
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