Journal article
Palmitate increases L-type Ca2+ currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells.
- Abstract:
- 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 status:
- Published
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- Publisher copy:
- 10.1113/jphysiol.2004.066258
Authors
- Journal:
- Journal of physiology More from this journal
- Volume:
- 557
- Issue:
- Pt 3
- Pages:
- 935-948
- Publication date:
- 2004-06-01
- DOI:
- EISSN:
-
1469-7793
- ISSN:
-
0022-3751
- Language:
-
English
- Keywords:
-
- Pubs id:
-
pubs:17353
- UUID:
-
uuid:03ddd166-7c8b-45a1-b8b5-64b35c30e32f
- Local pid:
-
pubs:17353
- Source identifiers:
-
17353
- Deposit date:
-
2012-12-19
- ARK identifier:
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- Copyright date:
- 2004
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