DPP-4 Inhibitor Sitagliptin Improves Cardiac Function and Glucose Homeostasis and Ameliorates β-Cell Dysfunction Together with Reducing S6K1 Activation and IRS-1 and IRS-2 Degradation in Obesity Female Mice

• Main Authors: Shigang Qiao, Guofang Mao, Hua Li, Zhimin Ma, Lei Hong, Huiling Zhang, Chen Wang, Jianzhong An
• Format: Article
• Language: English
• Published: Hindawi Limited 2018-01-01
• Series: Journal of Diabetes Research
• Online Access: http://dx.doi.org/10.1155/2018/3641516
• ISSN: 2314-6745; 2314-6753

Background. Chronic overnutrition leads to cardiac dysfunction and insulin (INS) resistance. Dipeptidyl peptidase-4 (DPP-4) improves glucose metabolism and insulin sensitivity in both human and animal models. In this study, we explored whether DPP-4 inhibitor sitagliptin (SIT) is involved in the protection of cardiac function and β-cell function using an obesity female mouse model. Methods. Six-week-old C57BL6/J mice were fed a high fat and fructose Western diet with DPP-4 inhibitor SIT for 12 weeks. Cardiac function was examined by echocardiography. Body weight, plasma glucose, and insulin concentrations were measured. The contents of total S6 kinase 1 (S6K1), phosphorylation of S6K1 activation, and INS docking proteins INS receptor substrates 1 and 2 (IRS-1, IRS-2) were assayed, and histology of heart tissue was performed. Results. Chronic Western diet consumption elevated plasma glucose and insulin and caused obesity, diastolic dysfunction, and β-cell dysfunction. DPP-4 inhibition with SIT resulted in reduction in body weight, fasting glucose, and plasma insulin, and improved cardiac diastolic dysfunction. SIT also decreased mTOR/S6K1 activation and prevented the degradation of IRS-1 and IRS-2. Conclusions. This study revealed pleiotropic protective effects of DPP-4 inhibitor SIT on cardiac function, glycemia, and β-cell function together with reducing S6K1 activation and IRS-1 and IRS-2 degradation in the obesity female mouse model.