The circadian system generates endogenous rhythms of approximately 24 hours that are vital for bodily functions. The circadian system coordinates many daily physiological processes, including glucose metabolism, cardiovascular function and thermoregulation. This system consists of a central clock in the suprachiasmatic nucleus (SCN) in the hypothalamus and peripheral clocks in tissues such as muscle, adipose tissue, liver and pancreas. The peripheral clock in the pancreas regulates insulin secretion; the peripheral clocks in muscle, adipose tissue and liver regulate local insulin sensitivity; and the peripheral clock in the intestine regulates glucose absorption.
The generation and maintenance of circadian rhythms is based on a transcriptional translational feedback loop. This feedback loop is regulated by the core clock genes CLOCK, BMAL1 transcriptional activators and Period (Per 1-2) and Cryptochrome (Cry 1-2) repressor genes. With modern life, shifting working hours, night shifts and sleep disorders cause changes in internal rhythms. The risk of various diseases such as insulin resistance, diabetes, obesity, cardiovascular system, digestive system diseases, cancer and neurodegenerative diseases increases due to the mismatch between central and peripheral clocks, disruption of the harmony of activities with circadian clocks and metabolic rhythms and mutations in circadian clock genes. Type 2 Diabetes Mellitus (Type 2 DM) is a metabolic disease in which hyperglycemia and dyslipidemia are observed as a result of impaired lipid and glucose metabolism due to tissue resistance to insulin action and deficiencies in insulin secretion from pancreatic β cells.
Disruption of circadian rhythms is known to be an all around trigger for the development of Type 2 diabetes, leading to accelerated diabetes development, impaired glucose-stimulated insulin secretion, and decreased β-cell mass. In addition, mutations in intracellular circadian clock genes such as CLOCK and BMAL1 increase β-cell failure and accelerate the development of diabetes. Improving the synchronization between diet, sleep-wake cycle, hormonal and autonomic rhythms, and central and peripheral clock rhythms is important to prevent and treat insulin resistance and type 2 diabetes.
Lecturer Aslıhan Şeyda Doğan
Faculty of Medicine
Department of Medical Pharmacology
