Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells.
10.3803/EnM.2018.33.1.105
- Author:
Seok Woo HONG
1
;
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
Author Information
1. Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Pioglitazone;
Insulin-secreting cells;
Glucolipotoxicity;
Inflammation;
Endoplasmic reticulum stress
- MeSH:
Animals;
Apoptosis;
Blood Glucose;
Caspase 3;
Chemokine CCL2;
Cytokines;
Diabetes Mellitus;
Endoplasmic Reticulum Stress*;
Endoplasmic Reticulum*;
Glucose Transport Proteins, Facilitative;
Humans;
Inflammation*;
Insulin;
Insulin Resistance;
Insulin-Secreting Cells;
Insulinoma;
Interleukin-6;
Islets of Langerhans;
Mice;
Necrosis;
Obesity;
Peptide Initiation Factors;
Peroxisomes;
Repression, Psychology;
Transcription Factors
- From:Endocrinology and Metabolism
2018;33(1):105-113
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ 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 α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, 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 ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus
