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Fatty acid‐induced effect on glucagon secretion is mediated via fatty acid oxidation
Author(s) -
Hong Jing,
Jeppesen Per Bendix,
Nordentoft Iver,
Hermansen Kjeld
Publication year - 2007
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.663
Subject(s) - carnitine , triglyceride , glucagon , fatty acid , medicine , beta oxidation , endocrinology , chemistry , secretion , biochemistry , biology , cholesterol , hormone
Background While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well‐defined, only limited information is available on alpha cells. This study evaluates the long‐term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation. Methods Clonal alpha cells were cultured with fatty acids in the presence of high glucose for up to 3 days. The influence of fatty acids on glucagon secretion, glucagon content and triglyceride accumulation from 24 to 72 h was investigated. After a − 72 h culture, cell proliferation, carnitine palmitoyl transferase‐1 mRNA level and the effect of etomoxir were also elucidated. Results Fatty acids stimulated glucagon secretion and increased triglyceride accumulation in a time‐ and dose‐dependent manner, but inhibited alpha cell proliferation. Lower concentrations (0.125–0.25 m M ) of fatty acids significantly increased glucagon secretion at 48 and 72 h, but did not affect triglyceride content. However, a marked increment in triglyceride accumulation occurred in the presence of 0.5 m M fatty acids. Fatty acids caused an up‐regulation of the expression of carnitine palmitoyl transferase‐1 gene. Etomoxir (1 µ M ) reversed fatty acid‐induced glucagon hypersecretion, but did not inhibit carnitine palmitoyl transferase‐1 mRNA level. Conclusions Our data indicates that compared with triglyceride accumulation, glucagon secretion is more sensitive to changes in fatty acid concentration. The effect of fatty acids on the glucagon response is mediated through their oxidation. The high carnitine palmitoyl transferase‐1 gene expression and the accumulation of triglyceride may initially be a compensatory oxidation reaction to elevated fatty acids. Copyright © 2006 John Wiley & Sons, Ltd.