2. Academic Validation
  3. Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells

Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells

  • J Diabetes Res. 2019 Feb 3;2019:5245063. doi: 10.1155/2019/5245063.
Kongbo Zhu 1,  Linglin Qian 1,  Yanshan Lin 2,  Li An 2,  Guangjian Mu 2,  Genshan Ma 1,  Liqun Ren 1 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing 210009, China.
  • 2 Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing 210009, China.
PMID: 30863781 DOI: 10.1155/2019/5245063
Abstract

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.

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