摘要：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
Bmal1 in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The
Sim1-
Cre-mediated deletion of
Bmal1 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
Avp in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed
Avp expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains
Avp 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
Avp expression is regulated by feeding, but not by PVN BMAL1.
