We recently showed that the CDK4-pRB-E2F1 cell cycle regulators directly regulate the expression of Kir6.2, which is a key component of the K(ATP) channel involved in the regulation of glucose-induced insulin secretion. There is enough evidence to indicate that the CDK4-pRB-E2F1 regulatory pathway is involved in general glucose homeostasis, and metabolism. In this article we discuss which are the metabolic implications of these findings.