Abstract

Brain almost solely depends on glucose for its source of energy. Therefore, it is its vested interest to ensure the mainte- nance of glucose level at a normal physiological range, thereby ensuring the continuous adequate supply of glucose to brain cells. With recent studies, it is reported that glucose homeostasis is not only regulated by the pancreatic islets but also by a brain-centered glucoregulatory system (BCGS). Studies on glucose-sensitive neurons have implicated their role in counterregulation and meal initiation and termination. This review explores the mechanisms by which the hepatic glucose production (HGP) and systemic glucose homeostasis is controlled by insulin-dependent indirect pathway and insulin-independent glucose disposal mechanisms via the BCGS. The review also discusses the impact of a two-system control that includes the pancreatic islet and the BCGS on diabetes mellitus.