title: Pioglitazone attenuates the detrimental effects of advanced glycation end-products in the pancreatic beta cell line HIT-T15.
abstract: Pioglitazone is an anti-diabetic agent that preserves pancreatic beta cell mass and improves their function. Advanced Glycation End-Products (AGEs) are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The aim of this work was to investigate the effects of Pioglitazone on the function and viability of HIT-T15 cells cultured with AGEs. HIT-T15 cells were cultured for 5 days in the presence of AGEs alone, or supplemented with 1 μmol/l Pioglitazone. Cell viability, insulin secretion and insulin content, redox balance, expression of the AGE receptor (RAGE), and NF-kB activation were then determined. The results showed that Pioglitazone protected beta cells against AGEs-induced apoptosis and necrosis. Moreover, Pioglitazone restored the redox balance and improved the responsiveness to low glucose concentration. Adding Pioglitazone to the AGEs culture attenuated NF-kB phosphorylation, and prevented AGEs to down-regulate IkBα expression. These findings suggest that Pioglitazone protects beta cells from the dangerous effects of AGEs.
authors.affiliation: University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 6, 16132 Genova, Italy. alep100@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Puddu
authors.forename: R
authors.initials: R
authors.lastname: Sanguineti
authors.forename: A
authors.initials: A
authors.lastname: Durante
authors.forename: G L
authors.initials: GL
authors.lastname: Viviani
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003470:Culture Media / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D000077205:Pioglitazone; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D017127:Glycation End Products, Advanced; D007328:Insulin; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D005978:Glutathione; D005947:Glucose; D000077205:Pioglitazone