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A novel combination of sitagliptin and melatonin ameliorates T2D manifestations: studies on experimental diabetic
R Patel1, N Parmar1, S P Palit1
1Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390002, India.
Introduction:
Type 2 diabetes (T2D) is an endocrine disorder characterized by hyperglycemia, insulin resistance, dysregulated glucose and lipid metabolism, reduced pancreatic β-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 β-cell proliferation under gluco-lipotoxicity stress in vitro.
Methods:
For 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.
Results:
Our 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 β-cell mass was preserved in all the drug-treated groups.
Conclusion:
The combination treatment is superior to monotherapies in the management of T2D.
Insights
Combining melatonin and sitagliptin effectively manages type 2 diabetes (T2D) by improving metabolic parameters and preserving pancreatic beta-cell mass. This combination therapy shows superior results compared to individual treatments for T2D.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Pharmacology
Background:
- Type 2 diabetes (T2D) involves hyperglycemia, insulin resistance, and impaired glucose/lipid metabolism.
- Disrupted circadian rhythms are linked to an increased risk of T2D.
- Investigated the therapeutic potential of melatonin (M) and sitagliptin (S), a DPP-IV inhibitor, for T2D management.
Purpose of the Study:
- To evaluate the combined therapeutic effects of melatonin and sitagliptin on T2D manifestations.
- To assess the impact of this combination on beta-cell proliferation under gluco-lipotoxicity stress.
- To compare the efficacy of combination therapy against monotherapies in a mouse model.
Main Methods:
- Induced T2D in mice using a high-fat diet (HFD) for 25 weeks.
- Treated mice with monotherapies (M or S) and combination therapy (S+M) for four weeks.
- Utilized primary mouse islets exposed to gluco-lipotoxic stress for in vitro studies.
Main Results:
- Combination therapy and monotherapies improved metabolic parameters and liver/adipose tissue glyco-lipid metabolism.
- Enhanced mitochondrial function in skeletal muscle and increased peripheral insulin sensitivity.
- Beta-cell mass was preserved in all drug-treated groups, both in vivo and in vitro.
Conclusions:
- The combination of melatonin and sitagliptin demonstrated superior efficacy in managing T2D compared to monotherapies.
- This combination therapy offers a promising strategy for T2D management.
- Preservation of beta-cell mass is a key benefit of the combined treatment.
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