A novel therapeutic combination of sitagliptin and melatonin regenerates pancreatic β-cells in mouse and human islets.

Autor: Patel R; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India., Parmar N; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India., Rathwa N; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India., Palit SP; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India., Li Y; Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Garcia-Ocaña A; Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Begum R; Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara- 390002, Gujarat, India. Electronic address: rasheedunnisab@yahoo.co.in.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2022 Aug; Vol. 1869 (8), pp. 119263. Date of Electronic Publication: 2022 Mar 29.
DOI: 10.1016/j.bbamcr.2022.119263
Abstrakt: Autoimmune-led challenge resulting in β-cell loss is responsible for the development of type 1 diabetes (T1D). Melatonin, a pineal hormone or sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, has increased β-cell mass in various diabetic models and has immunoregulatory property. Both β-cell regenerative capacity and melatonin secretion decrease with ageing. Thus, we aimed to investigate the therapeutic potential of melatonin combined with sitagliptin on β-cell regeneration under glucotoxic stress, in the streptozotocin-induced young and old diabetic mouse models, and euglycemic humanized islet transplant mouse model. Our results suggest that combination therapy of sitagliptin and melatonin show an additive effect in inducing mouse β-cell regeneration under glucotoxic stress, and in the human islet transplant mouse model. Further, in the young diabetic mouse model, the monotherapies induce β-cell transdifferentiation and reduce β-cell apoptosis whereas, in the old diabetic mouse model, melatonin and sitagliptin induce β-cell proliferation and β-cell transdifferentiation, and it also reduces β-cell apoptosis. Further, in both the models, combination therapy reduces fasting blood glucose levels, increases plasma insulin levels and glucose tolerance and promotes β-cell proliferation, β-cell transdifferentiation, and reduces β-cell apoptosis. It can be concluded that combination therapy is superior to monotherapies in ameliorating diabetic manifestations, and it can be used as a future therapy for β-cell regeneration in diabetes patients.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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