title: Pioglitazone ameliorates palmitate induced impairment of mitochondrial morphology and function and restores insulin level in beta cells.
abstract: This study aimed to investigate the effect of pioglitazone (PIO) on insulin secretion and mitochondrial ultrastructure and function in 3 cells. HIT-T15 cells were treated with control or palmitate (free fat acids, FFA) or/and PIO and divided into 7 groups: Control group; 0.5 mmol/l FFA (LF); 0.5 mmol/l FFA plus 10-7 mol/I PIO (LFLP); 0.5 mmol/l FFA plus 10-5mol/I PIO (LFHP); 1.0 mmol/l FFA (HF); 1.0 mmol/l FFA plus 10-7mol/I PIO (HFLP); 1.0 mmol/l FFA plus 10-5 mol/I PIO (HFHP). Apoptotic peaks, mitochondrial ultrastructure, ATP/ADP, mRNA levels of peroxisome proliferater activated receptor gamma coactivator-1 (PGC-1) and nucleus respiratory factor-1 (NRF-1) as well as insulin secretion were measured. The results showed that palmitate impaired mitochondrion structure, which could be alleviated by PIO. Palmitate could increase apoptotic peaks, decrease ATP/ADP ratio, enhance the expression of PGC-1 mRNA and NRF-1 mRNA, and decrease glucose stimulated insulin secretion (GSIS). In contrast, PIO could decrease apoptotic peaks, restore partly ATP/ADP ratio, decrease the expression of PGC-1 mRNA and NRF-1 mRNA, and increase GSIS level. These results demonstrate that PIO could ameliorate palmitate induced damage to mitochondrion ultrastructure and function and restore GSIS, accompanied by the modulation of PGC-1 and NRF-1 expression. These findings provide new insight into the hypoglycemic effects of PIO and help develop new agents for diabetes therapy.
authors.affiliation: The First Affiliated Hospital of Chengdu Medical College, Huaxi Hospital of Sichuan University, Chengdu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Xinxia
authors.initials: X
authors.lastname: Zhang
authors.forename: Nanwei
authors.initials: N
authors.lastname: Tong
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure*; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis; D010168:Palmitates / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077205:Pioglitazone; D060888:Real-Time Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D007328:Insulin; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; C486497:PPARGC1A protein, human; D010168:Palmitates; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D045162:Thiazolidinediones; D014157:Transcription Factors; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000077205:Pioglitazone