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Free fatty acids increase PGC‐1α expression in isolated rat islets
Author(s) -
Zhang Peixiang,
Liu Chang,
Zhang Chunni,
Zhang Yan,
Shen Pingping,
Zhang Junfeng,
Zhang Chen-Yu
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.046
Subject(s) - medicine , endocrinology , hyperlipidemia , downregulation and upregulation , palmitic acid , islet , diabetes mellitus , insulin , messenger rna , gene expression , oleic acid , carbohydrate metabolism , biology , pancreatic islets , metabolism , chemistry , fatty acid , biochemistry , gene
PGC‐1α mRNA and protein are elevated in islets from multiple animal models of diabetes. Overexpression of PGC‐1α impairs glucose‐stimulated insulin secretion (GSIS). However, it is not well known which metabolic events lead to upregulation of PGC‐1α in the β‐cells under pathophysiological condition. In present study, we have investigated effects of chronic hyperlipidemia and hyperglycemia on PGC‐1α mRNA expression in isolated rat islets. Isolated rat islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose‐dependently increases PGC‐1α mRNA expression level in isolated islets. FFA also increases PGC‐1α expression in mouse β‐cell‐derived βTC3 cell line. In contrast, 25 mM glucose decreases expression level of PGC‐1α. Inhibition of PGC‐1α by siRNA improves FFA‐induced impairment of GSIS in islets. These data suggest that hyperlipidemia and hyperglycemia regulate PGC‐1α expression in islets differently, and elevated PGC‐1α by FFA plays an important role in chronic hyperlipidemia‐induced β‐cell dysfunction.