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Glitazone‐like action of glimepiride and glibenclamide in primary human adipocytes
Author(s) -
Mayer P.,
Haas B.,
Celner J.,
Enzmann H.,
Pfeifer A.
Publication year - 2011
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01409.x
Subject(s) - glimepiride , glibenclamide , endocrinology , adipocyte , pioglitazone , medicine , adipogenesis , insulin resistance , peroxisome proliferator activated receptor , adiponectin , oil red o , chemistry , insulin , biology , receptor , adipose tissue , diabetes mellitus , type 2 diabetes
Aim: Sulphonylureas (SUs) are among the most widely used oral hypoglycaemic drugs that stimulate insulin secretion. In addition, SUs have pleiotropic effects on other tissues. Conflicting findings have been reported regarding the effects of SUs on adipocytes. We have now investigated the actions of glimepiride and glibenclamide (=glyburide) in primary human adipocytes. Methods: Primary cultured human white pre‐adipocytes were differentiated in vitro according to a standard protocol. Lipid accumulation was assessed by Oil Red O staining and determination of triglyceride content; gene expression was measured by RT PCR 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 and chemokine expression was decreased. Interestingly, the effects of SUs were generally qualitatively and quantitatively similar to those of pioglitazone. In direct comparison, glibenclamide was more potent than glimepiride with respect to the induction of fatty acid binding protein 4 (FABP4) (EC 50 0.32 vs. 2.8 µM), an important adipocyte marker gene. SU‐induced differentiation was virtually completely blocked by the peroxisome proliferator‐activated receptor γ (PPAR γ )‐antagonist T0070907 but not affected by diazoxide, indicating PPAR γ 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 γ . Thus, SUs but not repaglinide may be used to influence insulin resistance beyond their effect on insulin liberation.