Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells
| Autor: | Li An, Yanshan Lin, Linglin Qian, Kongbo Zhu, Liqun Ren, Guangjian Mu, Genshan Ma |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Article Subject Endocrinology Diabetes and Metabolism Atorvastatin Nerve Tissue Proteins lcsh:Diseases of the endocrine glands. Clinical endocrinology Cell Line Receptors G-Protein-Coupled Islets of Langerhans Endocrinology Insulin resistance Downregulation and upregulation Insulin-Secreting Cells Internal medicine Free fatty acid receptor 1 Diabetes mellitus Basic Helix-Loop-Helix Transcription Factors medicine Animals Hypoglycemic Agents Insulin Homeodomain Proteins NeuroD geography lcsh:RC648-665 geography.geographical_feature_category Pioglitazone business.industry nutritional and metabolic diseases Islet medicine.disease Rats Trans-Activators Hydroxymethylglutaryl-CoA Reductase Inhibitors Insulin Resistance business Research Article medicine.drug |
| Zdroj: | Journal of Diabetes Research Journal of Diabetes Research, Vol 2019 (2019) |
| ISSN: | 2314-6753 2314-6745 |
| Popis: | Increasing evidence shows that statins increase the risk of new-onset diabetes mellitus, but the exact mechanism is not clearly known. Free fatty acid receptor 1 (FFA1) has been recognized to mediate insulin secretion, and pioglitazone has direct effects on glucose-stimulated insulin secretion in addition to the reversion of insulin resistance. In this study, we found that atorvastatin decreased potassium-stimulated insulin secretion and inhibited the expression of FFA1, PDX-1, and BETA2/NeuroD in INS-1 cells. Further study demonstrated that pioglitazone prevented the impairment of insulin secretion induced by atorvastatin and enhanced the expression of FFA1, PDX-1, and BETA2/NeuroD reduced by atorvastatin in INS-1 cells. In addition, the preventive effect of pioglitazone on atorvastatin-induced impairment of insulin secretion and the enhancement of the expression of PDX-1 and BETA2/NeuroD was abolished by knockdown of FFA1 using siRNA or the PLC inhibitor, U-73122, respectively. Ultimately, FFA1 may mediate the atorvastatin-induced pancreatic β-cell dysfunction and pioglitazone may ameliorate this deleterious effect through the upregulation of FFA1 expression. |
| Databáze: | OpenAIRE |
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