Progressive deterioration of β-cell function and mass is a central parameter to the development of type-1/2 diabetes (T1/2D). Over the last decade, many studies have explored the potential benefits of incretin-based therapies on β-cell preservation and/or regeneration. In this context, DPP-IV inhibitor is known to improve GLP-1 and GIP longevity besides increasing β-cell mass. Melatonin, a pineal hormone is shown to ameliorate oxidative stress and bring about insulin secretion via MT1 receptor activation. Our aim was to evaluate the additive therapeutic effect of melatonin and DPP-IV inhibitor (sitagliptin) on β-cell regeneration in chemically (streptozotocin) induced T1D young and old mouse models, and on insulin resistance in high-fat diet (HFD)-induced T2D mouse model. Our results on pancreatic β-cell regeneration in T1D young and old mice suggest that the combinatorial treatment significantly increased insulin levels thereby lowering FBG levels and increasing glucose tolerance. In young diabetic mice, sitagliptin and melatonin work in an additive manner by increasing β-cell mass (replication and neogenesis) and decreasing apoptosis thus, ameliorating TID manifestations. However, in old diabetic mice, melatonin treatment alone was not as effective as sitagliptin treatment but a significant additive effect was observed in S+M group on β-cell regeneration. In HFD-induced T2D mice the combination therapy was superior to monotherapies in reducing FBG levels, and increasing glucose tolerance. Further, the combination treatment showed increased glucose metabolism, glycogen synthesis, and insulin sensitivity. There was no significant change in β-cell mass in HFD-induced T2D mice.

In conclusion, combinatorial therapy is able to ameliorate T1D and T2D in mouse models by β-cell regeneration and increasing insulin sensitivity. Melatonin promotes β-cell proliferation whereas sitagliptin promotes β-cell neogenesis and in concert, they enhance β-cell regeneration.


R. Patel: None. S. Pramanik: None. N.N. Rathwa: None. N.R. Parmar: None. H. Dhimmar: None. D.A. Pancholi: None. R. A.v.: None. R. Begum: None.


Department of Biotechnology, New Delhi, India (BT/PR12584/MED/31/289/2014)

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