期刊
DIABETES OBESITY & METABOLISM
卷 13, 期 9, 页码 791-799出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1463-1326.2011.01409.x
关键词
adipocytes; diabetes mellitus; drug mechanism; glitazones; sulphonylureas
Aim: Sulphonylureas (SUs) are amoug the most widely used oral hypoglycaemic drugs that simulate insulin secretion. In addition, SUs have pleiotropic effects on other tissues. Conflicting findings have been reported regarding the effects of SUs oil adipocytes. We have now ions of glimepiride and glibenclamide (=glyburide) in primary human adipocytes. Methods: Primary cultured human white pre-adipocytes were differentiated a vitro according to a standard protocol. Lipid accumulation was assessed by Oil Red 0 staining and determination of triglyceride content; gene expression was measured by RI PER and Western blotting. Results: Initially; we characterized the genes regulated during human pre-adipocyte differentiation by performing global microarray analysis. Treatment with glimepiride and glibenclamide caused an increased accumulation of lipid droplets and triglycerides. In addition, genes involved in lipid metabolism were induced mid chemokine expression was decreased. Interestingly, the effects of SIN were generally qualitatively and quantitatively similar to those of pioglitazone. In direct comparison, glibenclamide was inure potent than glimepiride with respect to the induction of fatty Kid binding protein 4 (FABP4) (FC(50) 0.32 vs. 2.8 mu M), an important adipocyte marker gene. SU-induced differentiation was ally completely blocked by the peroxisome proliferator-activated receptor gamma (PPAR gamma)-antagonist 10070907 but not affected by diazoxide, indicating PPAR gamma activation by SUs. Repaglinide had no effect on adipogenesis; although it causes insulin liberation like SUs. Conclusions: In primary human pre-adipocytes, glibenclamide and glimepiride strongly induced differentiation, apparently by activating PPAR gamma. Thus, SUs but not repaglinide may be used to influence insulin resistance beyond their effect on insulin liberation.
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