Oleic Acid Glucose-independently Stimulates Glucagon Secretion by Increasing Cytoplasmic Ca2+ Via Endoplasmic Reticulum Ca2+ Release and Ca2+ Influx in the Rat Islet Alpha-cells.
From: Department of Integrative Physiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
Endocrinology
- Publish Date: May 2007
- ISSN: 0013-7227
- Volume: 148
- Issue: 5
- Pages: 2496-504
- Medium: Print
- Language: English
- Citation (JAMA): Fujiwara Ken, Maekawa Fumihiko, Dezaki Katsuya, et al. Oleic Acid Glucose-independently Stimulates Glucagon Secretion by Increasing Cytoplasmic Ca2+ Via Endoplasmic Reticulum Ca2+ Release and Ca2+ Influx in the Rat Islet Alpha-cells.. Endocrinology May 2007;148:2496-504
Abstract
The effect of long-chain free fatty acids on glucagon secretion from islet alpha-cells has been a controversial issue. This study examined direct effects of oleic acid (OA) on glucagon release from rat pancreatic islets and on cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in single alpha-cells by fura-2 fluorescence imaging. OA at 30 microM increased glucagon release from isolated islets in the presence of low (2.8 mM) and elevated (8.3 mM) glucose concentrations. OA at 6-10 microm concentration-dependently increased [Ca(2+)](i) in alpha-cells, irrespective of glucose concentrations (1.4, 2.8, and 8.3 mM). OA at 10 mum increased [Ca(2+)](i) in 90% of alpha-cells. OA-induced [Ca(2+)](i) increases were strongly inhibited by the endoplasmic reticulum Ca(2+)-pump inhibitors cyclopiazonic acid and thapsigargin and by 2-aminoethoxydiphenyl borate, the blocker of both inositol 1,4,5-trisphosphate receptors and store-operated Ca(2+) channels. Furthermore, the amplitude, but not incidence, of OA-induced [Ca(2+)](i) increases was reduced substantially by Ca(2+)-free conditions and mildly by an L-type Ca(2+) channel blocker, nitrendipine, and an ATP-sensitive K(+) channel activator, diazoxide. OA-induced glucagon release was also inhibited mildly by nitrendipine and strongly by 2-aminoethoxydiphenyl borate. These results indicate that OA glucose-independently stimulates glucagon release by increasing [Ca(2+)](i) in rat pancreatic alpha-cells and that the [Ca(2+)](i) increase is triggered by Ca(2+) release from endoplasmic reticulum and amplified by Ca(2+) influx possibly via store-operated channels and via voltage-dependent L-type Ca(2+) channels. The glucose-independent action of OA to stimulate glucagon release from alpha-cells may operate under hypoglycemic conditions when plasma free fatty acids levels are elevated, possibly playing a role in maintaining glucose metabolism.
Mesh Headings (Keywords): Animals, Boron Compounds, Calcium, Cytoplasm, Dose-Response Relationship, Drug, Endoplasmic Reticulum, Enzyme Inhibitors, Fluorescent Dyes, Fura-2, Glucagon, Glucagon-Secreting Cells, Glucose, Indoles, Oleic Acid, Rats, Rats, Wistar, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Signal Transduction, Thapsigargin
Check for Full Text / PubMed Unique Identifier (PMID): 17289853
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.