insulin + melatonin

This is a combination of two hormones, insulin and melatonin, used experimentally in research settings for the management of diabetes and its complications. Insulin is a peptide hormone produced by pancreatic beta cells that regulates blood glucose by promoting cellular uptake of glucose and inhibiting hepatic glucose production. Melatonin is an indoleamine hormone produced by the pineal gland, primarily involved in regulating circadian rhythms and sleep-wake cycles via MT1 and MT2 receptors. In preclinical studies, combined administration of exogenous insulin and melatonin has shown synergistic effects in improving glycemic control, restoring altered hematological variables, enhancing insulin sensitivity in adipose tissue, reducing oxidative stress, normalizing pro-inflammatory cytokines, protecting against diabetic nephropathy (DN), and ameliorating metabolic abnormalities associated with diabetes[3][6][8]. The mechanism involves both direct metabolic actions (insulin receptor agonism) as well as modulation of circadian biology (melatonin receptor agonism), anti-oxidant activity from melatonin, improved β-cell function/regeneration potential from both agents together[3][6][8]. This combination has not been approved for clinical use but is under investigation in animal models.