title: Role of transient receptor potential melastatin-like subtype 5 channel in insulin secretion from rat β-cells.
abstract: OBJECTIVE
  Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca(2+)-activated monovalent cation channel, is involved in the stimulus-secretion coupling in the mouse pancreatic β-cells. We have studied the role of the TRPM5 channel in regulating insulin secretion and cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) in the rat β-cells by using triphenylphosphine oxide, a selective inhibitor of the channel.
  
  
  METHODS
  Insulin secretion from islets from Sprague-Dawley rats was measured in batch incubations. Cytoplasmic free Ca(2+) concentration was measured from single β-cells by fura-2-based microfluorometry.
  
  
  RESULTS
  Triphenylphosphine oxide did not alter insulin secretion and [Ca(2+)](i) response triggered by KCl or fructose. It inhibited insulin secretion in response to glucose, L-arginine, and glucagon-like peptide 1. It also inhibited glucose-induced insulin secretion by mechanisms that are independent of the adenosine triphosphate-sensitive potassium channels and [Ca(2+)](i) increase.
  
  
  CONCLUSIONS
  Our results suggest that in the rat islets, TRPM5 is involved in mediating insulin secretion by glucose and l-arginine and in potentiating the glucose-induced insulin secretion by glucagon-like peptide 1.
authors.affiliation: From the *Department of Clinical Science and Education, Karolinska Institutet, South Hospital, Stockholm, Sweden; †Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; and ‡Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Kalaiselvan
authors.initials: K
authors.lastname: Krishnan
authors.forename: Zuheng
authors.initials: Z
authors.lastname: Ma
authors.forename: Anneli
authors.initials: A
authors.lastname: Björklund
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Islam
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009943:Organophosphorus Compounds / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D007328:Insulin; D009943:Organophosphorus Compounds; D050053:TRPM Cation Channels; C571007:TRPM5 protein, rat; D052216:Glucagon-Like Peptide 1; D001120:Arginine; D005947:Glucose; D002118:Calcium; C063888:triphenylphosphine oxide