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bioRxiv · 10.1101/2025.03.17.639558

Melatonin and GABA monotherapies are as efficacious as combination therapy in managing T1D and T2D: In-vivo studies on experimental diabetic models

Parmar, N.·Patel, R.·Rathwa, N.·Dwivedi, M.·Begum, R.·Ramachandran, A. V.
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Abstract

BackgroundLoss of functional {beta}-cell mass is a critical factor in the ontogenesis of type 1 (T1D) and type 2 diabetes (T2D) marked by chronic hyperglycemia. Melatonin (M) and {gamma}-aminobutyric acid (GABA/G) have immunoregulatory properties and have shown potential to increase {beta}-cell mass in experimental diabetic models. Thus, we aimed to investigate the therapeutic potential of melatonin combined with GABA on {beta}-cell regeneration in streptozotocin (STZ)-induced T1D and on a high-fat diet (HFD)-induced T2D mouse models. MethodsThe BALB/c mice were injected with 50 mg/kg body weight STZ on five consecutive days to induce T1D and were subjected to six weeks of monotherapy with melatonin or GABA and combination therapy (M+G). HFD was fed to C57BL/6J mice for 30 weeks to induce insulin resistance and T2D, followed by six weeks of mono or combination therapy exposure. ResultsOur studies on monotherapies and combination therapy reduced fasting blood glucose levels, increased plasma insulin levels and glucose tolerance, and promoted {beta}-cell proliferation and transdifferentiation, with a simultaneous decrease in {beta}-cell apoptosis in T1D mice. It also improved metabolic parameters and glycolipid metabolism in the liver and adipose tissue, respectively, and increased mitochondrial function in the skeletal muscle. Moreover, it restored peripheral insulin sensitivity and {beta}-cell mass in T2D mice. ConclusionOur studies suggest that monotherapies are as effective as combination therapy since melatonin and GABA sub-additively ameliorates T1D and T2D manifestations.

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Parmar, N., Patel, R., Rathwa, N., Dwivedi, M., Begum, R., Ramachandran, A. V.. 2025-03-18. Melatonin and GABA monotherapies are as efficacious as combination therapy in managing T1D and T2D: In-vivo studies on experimental diabetic models. https://doi.org/10.1101/2025.03.17.639558

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