Diabetes mellitus and melatonin: Where are we?

Diabetes mellitus (DM) and diabetes-related complications are amongst the leading causes of mortality worldwide. The international diabetes federation (IDF) has estimated 592 million people to suffer from DM by 2035. Hence, finding a novel biomolecule that can effectively aid diabetes management is vital, as other existing drugs have numerous side effects. Melatonin, a pineal hormone having antioxidative and anti-inflammatory properties, has been implicated in circadian dysrhythmia-linked DM. Reduced levels of melatonin and a functional link between melatonin and insulin are implicated in the pathogenesis of type 2 diabetes (T2D). Additionally, genomic studies revealed that rare variants in melatonin receptor 1b (MTNR1B) are also associated with impaired glucose tolerance and increased risk of T2D. Moreover, exogenous melatonin treatment in cell lines, rodent models, and diabetic patients has shown a potent effect in alleviating diabetes and other related complications. This highlights the role of melatonin in glucose homeostasis. However, there are also contradictory reports on the effects of melatonin supplementation. Thus, it is essential to explore if melatonin can be taken from bench to bedside for diabetes management. This review summarizes the therapeutic potential of melatonin in various diabetic models and whether it can be considered a safe drug for managing diabetic complications and diabetic manifestations like oxidative stress, inflammation, ER stress, mitochondrial dysfunction, metabolic dysregulation, etc.