Activation of TRPV4 channel in pancreatic INS-1E beta cells enhances glucose-stimulated insulin secretion via calcium-dependent mechanisms

FEBS Lett. 2013 Oct 1;587(19):3281-7. doi: 10.1016/j.febslet.2013.08.025. Epub 2013 Aug 30.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Line
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • TRPV Cation Channels / metabolism*

Substances

  • Insulin
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Glucose
  • Calcium