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- Title
Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells.
- Authors
Seok-Woo Hong; Jinmi Lee; Jung Hwan Cho; Hyemi Kwon; Se Eun Park; Eun-Jung Rhee; Cheol-Young Park; Ki-Won Oh; Sung-Woo Park; Won-Young Lee
- Abstract
Background: The nuclear receptor peroxisome proliferator-activator gamma (PPAR?) is a useful therapeutic target for obesity and diabetes, but its role in protecting ß-cell function and viability is unclear. Methods: To identify the potential functions of PPAR? in ß-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPAR? agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. Results: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor a, interleukin 6 [IL-6], and IL-1ß) and ER stress markers (phosphor-eukaryotic translation initiation factor 2a, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6a, GRP78, and monocyte chemoattractant protein-1, prevented a-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in ß-cells. Moreover, the preservation of ß-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. Conclusion: Altogether, these results support the proposal that PPAR? agonists not only suppress insulin resistance, but also prevent ß-cell impairment via protection against ER stress and inflammation. The activation of PPAR? might be a new therapeutic approach for improving ß-cell survival and insulin secretion in patients with diabetes mellitus.
- Subjects
PIOGLITAZONE; PANCREATIC physiology; CELL physiology; THERAPEUTICS
- Publication
Endocrinology & Metabolism, 2018, Vol 33, Issue 1, p105
- ISSN
2093-596X
- Publication type
Article
- DOI
10.3803/EnM.2018.33.1.105