The role of brain in the regulation of glucose homeostasis (original) (raw)

2015, International Journal of Medical Science and Public Health

behavior but also glucose and energy homeostasis. [5] Renowned physiologist, Claude Bernard, was the first to propose a role for the brain in both glucose homeostasis and diabetes pathogenesis. In his famous experiment, "la pigȗrediabétique," he demonstrated the induction of diabetes resulting in glucosuria by puncturing the floor of the fourth ventricle in rabbits. [6] The discovery of insulin, in 1921, and the subsequent identification of liver, muscle, and adipose tissue as principal targets of the powerful effects of insulin on glucose metabolism has overshadowed the importance of brain in glucose homeostasis and prevented the complete understanding of the pathophysiology of diabetes mellitus. The current treatment of diabetes is islet centered and revolves around the role of insulin. Treatment includes, principally, recombinant human insulin preparations, insulin secretagogues, and drugs that increase insulin sensitivity. These drugs are effective in controlling hyperglycemia and in addressing the consequences of diabetes, but they fail to address the underlying cause; hence, they control rather than cure the disease. [7] The role of the brain to control glucose homeostasis was again brought to light, in 1964, when two laboratories reported neurons within the hypothalamus responding to changes in the plasma glucose. [8,9] Recent studies of glucose-sensitive neurons in the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamus, the arcuate nucleus, and even in the brain stem that possibly initiates counterregulatory response and Brain almost solely depends on glucose for its source of energy. Therefore, it is its vested interest to ensure the maintenance 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.