Premium
Palmitate increases L‐type Ca 2+ currents and the size of the readily releasable granule pool in mouse pancreatic β‐cells
Author(s) -
Olofsson Charlotta S.,
Salehi Albert,
Holm Cecilia,
Rorsman Patrik
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.066258
Subject(s) - exocytosis , palmitic acid , chemistry , pancreatic islets , biophysics , medicine , intracellular , secretagogue , insulin , endocrinology , beta cell , fatty acid , secretion , biochemistry , islet , biology
We have investigated the in vitro effects of the saturated free fatty acid palmitate on mouse pancreatic β‐cells by a combination of electrophysiological recordings, intracellular Ca 2+ ([Ca 2+ ] i ) microfluorimetry and insulin release measurements. Addition of palmitate (1 m m , bound to fatty acid‐free albumin) to intact islets exposed to 15 m m glucose increased the [Ca 2+ ] i by ∼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 m m ) augmented exocytosis (measured as an increase in cell capacitance) in single β‐cells and increased the size of the readily releasable pool (RRP) of granules 2‐fold. Whole‐cell peak Ca 2+ currents rose by ∼25% following addition of 0.5 m m palmitate, an effect that was abolished in the presence of 10 μ m 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.