@article{article_1431797, title={Sitagliptin does not improve isoprenaline-induced cardiac contractility in streptozotocin-induced diabetic rats}, journal={İstanbul Journal of Pharmacy}, volume={54}, pages={359–367}, year={2024}, DOI={10.26650/IstanbulJPharm.2024.1431797}, author={Uyar Boztas, Ceren and Erdoğan, Betül Rabia and Müderrisoğlu, Ayhanım Elif and Kaykı Mutlu, Gizem and Yeşilyurt Dirican, Zeynep Elif and Karaömerlioğlu, İrem and Altan, Vecdi Melih and Arıoğlu İnan, Ebru}, keywords={Beta adrenoceptor, Diabetes, Heart, Isoprenaline, Sitagliptin}, abstract={Background and Aims: Sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, has been shown to have beneficial effects on the diabetic heart. Beta-adrenoceptor (β-AR)-mediated responses are impaired in diabetes. Our aim was to investigate the impact of sitagliptin on the diabetic rat heart in terms of β-AR-mediated responsiveness. In addition, we examined the expression of proteins associated with diastolic dysfunction and endoplasmic reticulum (ER) stress, as well as proteins involved in the β-AR signalling pathway.
Methods: Eight-week-old Sprague-Dawley rats were divided into control, diabetic, and sitagliptin-treated (10 mg/kg/day for 4 weeks) diabetic groups. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (STZ). Throughout the treatment period, the rats received sitagliptin orally. Cardiac β-AR responsiveness was assessed using in vitro papillary muscle experiments with a nonselective β-AR agonist, isoprenaline, and in vitro Langendorff heart preparation experiments with a β3-AR selective agonist CL 316,243. Western blot experiments were conducted to assess the protein expression of SERCA2a, GRP78, β3-AR, eNOS, and p-eNOS.
Results: Sitagliptin did not reduce blood glucose levels or reverse weight loss in diabetic rats. However, it improved the heart weight to body weight ratio, indicating a reduction in cardiac hypertrophy. Sitagliptin did not correct the isoprenaline-induced contractile response in the diabetic group, nor did it alter the β3-AR mediated relaxation. Sitagliptin treatment also did not improve the downregulation of SERCA2a or the upregulation of GRP78. However, it reduced the upregulation of β3-AR. The protein expression of eNOS and the ratio of p-eNOS to eNOS were similar among the groups.
Conclusion: This study indicates that sitagliptin treatment did not improve isoprenaline-mediated contractile responses or affect β3-AR-mediated relaxation in the diabetic heart. However, the observed increase in β3-AR protein expression in the diabetic heart treated with sitagliptin indicated a potential differential effect of the drug on this pathway compared to the β1-AR signalling pathway. Further studies are needed to elucidate the precise mechanisms by which sitagliptin influences β3-AR-mediated pathways.}, number={3}, publisher={Istanbul University}