Type 2 diabetes is a complex disease mainly characterized by impaired insulin action and insulin secretion [1, 2]. A major breakthrough in the understanding of mechanisms leading to type 2 diabetes has recently come from studies on the central nervous system (CNS) dependent regulation of glucose and fat metabolism. The concept that the CNS has an essential role in glucose homeostasis and insulin action is not new. In 1849, Claude Bernard reported that pricking the floor of the fourth ventricle in rabbits produced hyperglycemia . The past decade has greatly increased knowledge about the ability of the CNS to regulate food intake, body weight and glucose homeostasis. It is now clear that the CNS, and in particular the hypothalamus, plays a pivotal role in regulating glucose homeostasis independently of its effects on body weight. Therefore, some of the molecular defects underlying type 2 diabetes may reside in the CNS, supporting the concept that type 2 diabetes is, at least in part, a hypothalamic disorder.