Curcumin induces electrical activity in rat pancreatic beta-cells by activating the volume-regulated anion channel.
Curcumin, the principal active component of turmeric, is reported to exert a number of therapeutic actions, including a hypoglycaemic/antidiabetic action. The underlying mechanisms to this action are essentially unknown. We have investigated the hypothesis that a direct stimulatory action on the pancreatic beta-cell could contribute towards the hypoglycaemic activity of this compound. Electrical and ion channel activity were recorded in rat beta-cells using the patch-clamp technique. beta-Cell volume was measured using a video-imaging technique. Insulin release was measured from intact islets by radioimmunoassay. Curcumin (2-10 microM) activated the volume-regulated anion channel in beta-cells. Single channel studies indicated that activation was the result of increased channel open probability. This effect was accompanied by depolarisation of the cell membrane potential, the generation of electrical activity and enhanced insulin release. Curcumin also decreased beta-cell volume, presumably reflecting loss of Cl(-) (and hence water) as a result of anion channel activation. These findings are consistent with the suggestion that Cl(-) fluxes play an important role in regulating beta-cell function. The stimulation of beta-cell function by curcumin could contribute to the hypoglycaemic actions of this compound, and these findings identify a novel potential therapeutic target for the treatment of type 2 diabetes mellitus.
Best
Leonard
L
Department of Medicine, University of Manchester, Oxford Road, Manchester M13 9WL, UK. Len.Best@cmmc.nhs.uk
Elliott
Austin C
AC
Brown
Peter D
PD
D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004553:Electric Conductivity; D005260:Female; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018118:Chloride Channels; D007328:Insulin; D003474:Curcumin