title: Activation of TRPV4 channel in pancreatic INS-1E beta cells enhances glucose-stimulated insulin secretion via calcium-dependent mechanisms.
abstract: Transient receptor potential channel vanilloid type 4 (TRPV4) is a Ca(2+)- and Mg(2+)-permeable cation channel that influences oxidative metabolism and insulin sensitivity. The role of TRPV4 in pancreatic beta cells is largely unknown. Here, we characterize the role of TRPV4 in controlling intracellular Ca(2+) and insulin secretion in INS-1E beta cells. Osmotic, thermal or pharmacological activation of TRPV4 caused a rapid rise of intracellular Ca(2+) and enhanced glucose-stimulated insulin secretion. In the presence of the TRPV channel blocker ruthenium red (RuR) or after suppression of TRPV4 protein production, TRPV4 activators failed to increase [Ca(2+)]i and insulin secretion in INS-1E cells.
authors.affiliation: Department of Hepatology and Gastroenterology, The Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, 13353 Berlin, Germany; Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, 60-637 Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Skrzypski
authors.forename: M
authors.initials: M
authors.lastname: Kakkassery
authors.forename: S
authors.initials: S
authors.lastname: Mergler
authors.forename: C
authors.initials: C
authors.lastname: Grötzinger
authors.forename: N
authors.initials: N
authors.lastname: Khajavi
authors.forename: M
authors.initials: M
authors.lastname: Sassek
authors.forename: D
authors.initials: D
authors.lastname: Szczepankiewicz
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: K W
authors.initials: KW
authors.lastname: Nowak
authors.forename: M Z
authors.initials: MZ
authors.lastname: Strowski
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D007328:Insulin; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D005947:Glucose; D002118:Calcium
keywords: 4α-PDD; Beta cell; Calcium; INS-1E; Insulin secretion; KRHB; Krebs–Ringer-HEPES buffer; PKC; TRP; TRPM2; TRPV4; cAMP; cyclic adenosine monophosphate; hIAPP; human islet amyloid polypeptide; non-targeting siRNA; nt siRNA; protein kinase C; siRNA; small interfering RNA; the phorbol ester 4α-phorbol 12,13-didecanoate; transient receptor potential cation channel subfamily V member 4; transient receptor potential cation channel, subfamily M, member 2; transient receptor potential channel