Cognitive impairment with diabetes mellitus and metabolic disease: innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways.
Limited information is available regarding the role of clock genes in the disruption of BP circadian rhythm in diabetes due to the lack of a diabetic animal model that allows real-time monitoring of clock gene oscillation.
Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo.
Variant of the CLOCK gene and related haplotypes are associated with the prevalence of T2D in the Japanese population, in which obesity is less common, and the association between CLOCK gene variant at rs1801260 and the prevalence of diabetes is enhanced in normal-weight subjects.
It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.
A series of our recent studies revealed that circadian clock proteins are important for hypofibrinolysis induced by metabolic disorders such as obesity and diabetes.
In this review, we discuss the following items: 1) circadian clock system, 2) effect of the diet on clock gene expression, 3) effect of clock mutation on lipid metabolism, and 4) effect of streptozotocin-induced diabetes and ob mutation on clock gene expression and lipid metabolism.