Multi-Omics Reveal Interplay between Circadian Dysfunction and Type2 Diabetes

SIMPLE SUMMARY: Type 2 diabetes (T2D), a metabolic disorder, characterized by dysregulated glucose metabolism. Circadian rhythms, nearly 24-h biological oscillations, control daily biological functions including glucose metabolism, that are essential for survival. Circadian arrythmia caused by irregular meal timing, and sleep loss alters glucose metabolism and insulin production can result in metabolic condition, T2D. Understanding dysregulated circadian metabolism using systems biology approaches may provide solutions to treat T2D. Using multi-omics approach, present work correlates how circadian arrythmia caused by T2D alters different genes, proteins and metabolites. ABSTRACT: Type 2 diabetes is one of the leading threats to human health in the 21st century. It is a metabolic disorder characterized by a dysregulated glucose metabolism resulting from impaired insulin secretion or insulin resistance. More recently, accumulated epidemiological and animal model studies have confirmed that circadian dysfunction caused by shift work, late meal timing, and sleep loss leads to type 2 diabetes. Circadian rhythms, 24-h endogenous biological oscillations, are a fundamental feature of nearly all organisms and control many physiological and cellular functions. In mammals, light synchronizes brain clocks and feeding is a main stimulus that synchronizes the peripheral clocks in metabolic tissues, such as liver, pancreas, muscles, and adipose tissues. Circadian arrhythmia causes the loss of synchrony of the clocks of these metabolic tissues and leads to an impaired pancreas β-cell metabolism coupled with altered insulin secretion. In addition to these, gut microbes and circadian rhythms are intertwined via metabolic regulation. Omics approaches play a significant role in unraveling how a disrupted circadian metabolism causes type 2 diabetes. In the present review, we emphasize the discoveries of several genes, proteins, and metabolites that contribute to the emergence of type 2 diabetes mellitus (T2D). The implications of these discoveries for comprehending the circadian clock network in T2D may lead to new therapeutic solutions.