Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism.

It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The --mediated deletion of markedly reduced insulin secretion, resulting in impaired glucose tolerance. The pancreatic islets' responses to glucose, sulfonylureas (SUs) and arginine vasopressin (AVP) were well maintained. To specify the PVN neuron subpopulation targeted by Bmal1, the expression of neuropeptides was examined. In these knockout (KO) mice, the mRNA expression of in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains expression in the PVN and release to the circulation, possibly providing islet β-cells with more AVP. This action helps enhance insulin release and, consequently, glucose tolerance. In contrast, the circadian variation of expression is regulated by feeding, but not by PVN BMAL1.