A novel combination of sitagliptin and melatonin ameliorates T2D manifestations: studies on experimental diabetic models

摘要

IntroductionType 2 diabetes (T2D) is an endocrine disorder characterized by hyperglycemia, insulin resistance, dysregulated glucose and lipid metabolism, reduced pancreatic beta-cell function and mass, and a reduced incretin effect. Circadian rhythm disruption is associated with increased T2D risk. We have investigated the therapeutic potential of a combination of melatonin (M) and sitagliptin (S), a dipeptidyl peptidase IV (DPP-IV) inhibitor, in the amelioration of T2D manifestations in high-fat diet (HFD) induced T2D mouse model and also on beta-cell proliferation under gluco-lipotoxicity stress in vitro.MethodsFor in vivo study, mice were fed with HFD for 25 weeks to induce T2D and were treated with monotherapies and S + M for four weeks. For the in vitro study, primary mouse islets were exposed to normal glucose and high glucose + palmitate to induce gluco-lipotoxic stress.ResultsOur results suggest that monotherapies and S + M improve metabolic parameters and glyco-lipid metabolism in the liver and adipose tissue, respectively, and improve mitochondrial function in the skeletal muscle. Moreover, it increases peripheral insulin sensitivity. Our in vitro and in vivo studies suggest that beta-cell mass was preserved in all the drug-treated groups.ConclusionThe combination treatment is superior to monotherapies in the management of T2D.