Central nervous system and control of endogenous glucose production

Recent evidence points to the crucial role of the central nervous system in controlling glucose homeostasis. Hypothalamic centers involved in the regulation of energy balance and endogenous glucose production constantly sense fuel availability by receiving and integrating inputs from circulating nutrients and hormones such as insulin and leptin. In response to these peripheral signals, the hypothalamus sends out efferent impulses that restrain food intake and endogenous glucose production. This promotes energy homeostasis and keeps blood glucose levels in the normal range. Disruption of this intricate neural control is likely to occur in type 2 diabetes and obesity and may contribute to defects of glucose homeostasis and insulin resistance common to both diseases. This review summarizes the latest findings on the hypothalamic control of endogenous glucose production, and focuses on the central effects of circulating macronutrients and nutrient-induced hormones.