Melatonin, Circadian Rhythms, and Type 2 Diabetes Mellitus: A Comprehensive Review of Epidemiology, Molecular Mechanisms, and Therapeutic Implications

Abstract

This extensive review delves into the epidemiology, risk factors, historical background, and molecular mechanisms of Type 2 Diabetes Mellitus (T2DM). The term "diabetes mellitus" dates back to ancient times and the Greek physician Aertaeus is credited with coining the term. T2DM, which is defined by hyperglycemia, insulin resistance, and relative insulin deficiency, is a global public health concern that affects millions of people worldwide. A combination of genetic, environmental, and lifestyle factors play a role in the development of T2DM. The distinction between Type 1 and Type 2 diabetes was established in 1936, and Type 2 diabetes was identified as a component of the metabolic syndrome in 1988. T2DM is becoming more and more common; it is expected to affect 552 million people by 2030, which means that research and interventions are desperately needed. The risk factors for T2DM include age, genetics, obesity, sedentary lifestyle, and components of the metabolic syndrome. Prediabetes, which is a precursor to T2DM, must be detected early in order to reduce the risk of progression. This review explores the physiological and molecular mechanisms underlying T2DM, with a focus on the complex interactions between melatonin, circadian rhythms, and diabetes. Melatonin, this is primarily synthesized by the pineal gland, is essential for the regulation of circadian rhythms and many other physiological processes. Research has shown how melatonin affects insulin secretion and glucose metabolism, suggesting that it may have therapeutic uses in the treatment of diabetes. Circadian rhythm disturbances, particularly those brought on by shift work, are linked to a higher risk of type 2 diabetes, underscoring the importance of comprehending these intricate relationships. The review highlights the need for more research to fully understand the complex relationships between melatonin, circadian rhythms, and diabetes. Pharmacological interventions, such as the synthetic melatonin agonist agomelatine, offer promising avenues for therapeutic exploration. Thapsigargin, an antagonist of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), reveals the role of calcium signaling in diabetes research.