PMID- 23700793 OWN - NLM STAT- MEDLINE DCOM- 20130626 LR - 20181202 IS - 0031-7144 (Print) IS - 0031-7144 (Linking) VI - 68 IP - 4 DP - 2013 Apr TI - Pioglitazone ameliorates palmitate induced impairment of mitochondrial morphology and function and restores insulin level in beta cells. PG - 270-3 AB - 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. FAU - Li, Yao AU - Li Y AD - The First Affiliated Hospital of Chengdu Medical College, Huaxi Hospital of Sichuan University, Chengdu, China. FAU - Zhang, Xinxia AU - Zhang X FAU - Tong, Nanwei AU - Tong N LA - eng PT - Journal Article PL - Germany TA - Pharmazie JT - Die Pharmazie JID - 9800766 RN - 0 (Heat-Shock Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Indicators and Reagents) RN - 0 (Insulin) RN - 0 (NRF1 protein, human) RN - 0 (Nuclear Respiratory Factor 1) RN - 0 (PPARGC1A protein, human) RN - 0 (Palmitates) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Thiazolidinediones) RN - 0 (Transcription Factors) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Adenosine Diphosphate/metabolism MH - Adenosine Triphosphate/metabolism MH - Apoptosis/drug effects MH - Cell Line MH - Chromatography, High Pressure Liquid MH - Flow Cytometry MH - Heat-Shock Proteins/biosynthesis MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - In Situ Nick-End Labeling MH - Indicators and Reagents MH - Insulin/*metabolism MH - Insulin-Secreting Cells/drug effects/*metabolism/ultrastructure MH - Microscopy, Electron MH - Mitochondria/drug effects/*ultrastructure MH - Nuclear Respiratory Factor 1/biosynthesis MH - Palmitates/*antagonists & inhibitors/*toxicity MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - Pioglitazone MH - Real-Time Polymerase Chain Reaction MH - Thiazolidinediones/*pharmacology MH - Transcription Factors/biosynthesis EDAT- 2013/05/25 06:00 MHDA- 2013/06/28 06:00 CRDT- 2013/05/25 06:00 PHST- 2013/05/25 06:00 [entrez] PHST- 2013/05/25 06:00 [pubmed] PHST- 2013/06/28 06:00 [medline] PST - ppublish SO - Pharmazie. 2013 Apr;68(4):270-3.