Palmitate increases L-type Ca2+ currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells

J Physiol. 2004 Jun 15;557(Pt 3):935-48. doi: 10.1113/jphysiol.2004.066258. Epub 2004 Apr 16.


We have investigated the in vitro effects of the saturated free fatty acid palmitate on mouse pancreatic beta-cells by a combination of electrophysiological recordings, intracellular Ca(2+) ([Ca(2+)](i)) microfluorimetry and insulin release measurements. Addition of palmitate (1 mm, bound to fatty acid-free albumin) to intact islets exposed to 15 mm glucose increased the [Ca(2+)](i) by approximately 30% and insulin secretion 2-fold. Palmitate remained capable of increasing [Ca(2+)](i) and insulin release in the presence of tolbutamide and in islets depolarized by high K(+) in combination with diazoxide, indicating that the stimulation occurs independently of closure of ATP-regulated K(+) channels (K(ATP) channels). Palmitate (0.5 mm) augmented exocytosis (measured as an increase in cell capacitance) in single beta-cells and increased the size of the readily releasable pool (RRP) of granules 2-fold. Whole-cell peak Ca(2+) currents rose by approximately 25% following addition of 0.5 mm palmitate, an effect that was abolished in the presence of 10 microm isradipine indicating that the free fatty acid specifically acts on L-type Ca(2+) channels. The actions of palmitate on exocytosis and Ca(2+) currents were not mimicked by intracellular application of palmitoyl-CoA. We conclude that palmitate increases insulin secretion by a K(ATP) channel-independent mechanism exerted at the level of exocytosis and that involves both augmentation of L-type Ca(2+) currents and an increased size of the RRP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / drug effects*
  • Cell Polarity / drug effects
  • Cell Separation
  • Cell Size
  • Cyclic AMP / physiology
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Electrophysiology
  • Exocytosis / drug effects
  • Female
  • Glucose / pharmacology
  • Insulin / metabolism
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • KATP Channels
  • Membrane Potentials / physiology
  • Mice
  • Palmitates / pharmacology*
  • Palmitoyl Coenzyme A / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Potassium Channels, Inwardly Rectifying
  • Serum Albumin, Bovine / pharmacology


  • ATP-Binding Cassette Transporters
  • Calcium Channels, L-Type
  • Insulin
  • KATP Channels
  • Palmitates
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • uK-ATP-1 potassium channel
  • Palmitoyl Coenzyme A
  • Serum Albumin, Bovine
  • Cyclic AMP
  • Glucose
  • Calcium