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Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta-cells.
Biochem Biophys Res Commun. 2010 Jan 15; 391(3):1567-72.BB

Abstract

Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor delta (PPARdelta) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic beta-cells. After HIT-T15 cells (a beta-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPARdelta), we found that administration of GW increased the expression of PPARdelta mRNA. GW-induced activation of PPARdelta up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPARdelta plays an important role in protecting pancreatic beta-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

Authors+Show Affiliations

Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20040361

Citation

Wan, Jun, et al. "Activation of PPARdelta Up-regulates Fatty Acid Oxidation and Energy Uncoupling Genes of Mitochondria and Reduces Palmitate-induced Apoptosis in Pancreatic Beta-cells." Biochemical and Biophysical Research Communications, vol. 391, no. 3, 2010, pp. 1567-72.
Wan J, Jiang L, Lü Q, et al. Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta-cells. Biochem Biophys Res Commun. 2010;391(3):1567-72.
Wan, J., Jiang, L., Lü, Q., Ke, L., Li, X., & Tong, N. (2010). Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta-cells. Biochemical and Biophysical Research Communications, 391(3), 1567-72. https://doi.org/10.1016/j.bbrc.2009.12.127
Wan J, et al. Activation of PPARdelta Up-regulates Fatty Acid Oxidation and Energy Uncoupling Genes of Mitochondria and Reduces Palmitate-induced Apoptosis in Pancreatic Beta-cells. Biochem Biophys Res Commun. 2010 Jan 15;391(3):1567-72. PubMed PMID: 20040361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta-cells. AU - Wan,Jun, AU - Jiang,Li, AU - Lü,Qingguo, AU - Ke,Linqiu, AU - Li,Xiaoyu, AU - Tong,Nanwei, Y1 - 2009/12/27/ PY - 2009/12/14/received PY - 2009/12/22/accepted PY - 2009/12/31/entrez PY - 2009/12/31/pubmed PY - 2010/2/23/medline SP - 1567 EP - 72 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 391 IS - 3 N2 - Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor delta (PPARdelta) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic beta-cells. After HIT-T15 cells (a beta-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPARdelta), we found that administration of GW increased the expression of PPARdelta mRNA. GW-induced activation of PPARdelta up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPARdelta plays an important role in protecting pancreatic beta-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/20040361/Activation_of_PPARdelta_up_regulates_fatty_acid_oxidation_and_energy_uncoupling_genes_of_mitochondria_and_reduces_palmitate_induced_apoptosis_in_pancreatic_beta_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(09)02513-3 DB - PRIME DP - Unbound Medicine ER -