DPP-4 Inhibitor Sitagliptin Improves Cardiac Function and Glucose Homeostasis and Ameliorates Œ≤-Cell Dysfunction Together with Reducing S6K1 Activation and IRS-1 and IRS-2 Degradation in Obesity Female Mice
Authors: Hua Li
Chen Wang
Shigang Qiao
Huiling Zhang
Jianzhong An
Lei Hong
Guofang Mao
Zhimin Ma
Journal: Journal of diabetes research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Chronic overnutrition; cardiac dysfunction; insulin resistance; Dipeptidyl peptidase-4 (DPP-4); glucose metabolism
Affiliations: Institute of Clinical Medicine Research, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Science and Technology Town Hospital, No. 1 Lijiang Road, Suzhou 215153, China., Department of Anesthesiology and Perioperative Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Science and Technology Town Hospital, No. 1 Lijiang Road, Suzhou 215153, China., Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, No. 199 Renai Road, Suzhou 215123, China., Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Science and Technology Town Hospital, No. 1 Lijiang Road, Suzhou 215153, China.

Abstract:  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 Œ≤-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 Œ≤-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 Œ≤-cell function together with reducing S6K1 activation and IRS-1 and IRS-2 degradation in the obesity female mouse model. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 3. * Green boxes: Panel a Sham looks remarkably similar to Figure 3A in another paper by the same group, i.e. Shi-gang Qiao et al. Acta Pharmac Sinica 2019, DOI: 10.1038 s41401-018-0066-y, https: pubpeer.com publications D0DFFFC63E15492138022BBA628807. In this paper, the panel represents heart tissue from six-week-old wild-type control (C57BLKS J) female mice fed a wild type diet. In the Acta Pharmac Sinica paper, the panel represents heart tissue from 9-12 week-old adult male Sprague-Dawley rats receiving a sham operation. Could the authors please provide a plausible explanation for what has happened here?  , 
 Figures 4 and 5. * Red boxes: The Ser636 p-IRIS-1 panel in Figure 4 looks very similar to the Ser731 p-IRS-2 panel in Figure 5, if one of the panels is flipped vertically.  Here is a close-up view of both panels, with one of the panels flipped vertically.  ,