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Pioglitazone attenuates fatty acid–induced oxidative stress and apoptosis in pancreatic β‐cells
Author(s) -
Saitoh Y.,
Chunping C.,
Noma K.,
Ueno H.,
Mizuta M.,
Nakazato M.
Publication year - 2008
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.1463-1326.2007.00749.x
Subject(s) - pioglitazone , medicine , endocrinology , lipotoxicity , oxidative stress , insulin resistance , insulin , chemistry , fatty acid , downregulation and upregulation , beta cell , intracellular , apoptosis , peroxisome proliferator activated receptor , triglyceride , diabetes mellitus , biology , receptor , islet , type 2 diabetes , biochemistry , cholesterol , gene
Aims: Thiazolidinediones (TZDs), ligands for peroxisome proliferator–activated receptor γ, are antidiabetic agents that improve hyperglycemia by decreasing insulin resistance in obese diabetic animal models and patients with type 2 diabetes. We have studied whether pioglitazone, a TZD, can exert a direct effect against pancreatic β‐cell lipoapoptosis. Methods: MIN6 cells were cultured in medium containing either 5.6 (low glucose) or 25 mM glucose (high glucose) in the presence or absence of 0.5 mM palmitate for 48 h. We examined the effect of 10 μM pioglitazone on MIN6 cells on glucose‐stimulated insulin secretion, cellular ATP, uncoupling protein‐2 (UCP‐2) mRNA expression, intracellular triglyceride content, reactive oxygen species production, the number of apoptotic cells and nuclear factor‐κB (NF‐κB) activity. Results: Pioglitazone recovered partly impaired glucose‐stimulated insulin secretion and cellular ATP in MIN6 cell exposed to high glucose with 0.5 mM palmitate. Pioglitazone suppressed intracellular triglyceride accumulation in cells exposed to high glucose with 0.5 mM palmitate. Palmitate‐induced upregulation of UCP‐2 mRNA levels was suppressed by pioglitazone in a dose‐dependent manner. Pioglitazone decreased palmitate‐induced reactive oxygen species production in MIN6 cells by 24% and in mouse islet cells by 53%. Pioglitazone also decreased palmitate‐induced NF‐κB activity by 40% and protected β‐cells from palmitate‐induced apoptosis by 22% in MIN6 cell. Conclusions: Pioglitazone attenuated fatty acid–induced oxidative stress and apoptosis in pancreatic β‐cells. TZDs might be used as a mean for maintaining β‐cell survival and preserving capacity of insulin secretion in patients with diabetes mellitus.