Is There Cross Talk Between Portal and Hypothalamic Glucose-Sensing Circuits?

The detection of hypoglycemia stems from sensors located in both the periphery and within the central nervous system and likely involves a complex circuit that incorporates information from both peripheral and central components. Glucose sensors located in each of these regions play a unique role in hypoglycemia detection that appears to be at least in part dependent on the rate of fall of blood glucose levels. Sensors that are located within the brain, particularly those located within the ventromedial hypothalamus (VMH), appear to dominate when glucose levels fall rapidly (1–3). While still speculative, it has been proposed that this may serve as a protective fail-safe mechanism that is put in place to prevent a sudden and potentially catastrophic depletion of fuel supply to the brain. On the other hand, glucose sensors located in the portal-mesenteric vein (PMV) have been proposed to be more important for detecting a gradual decline in blood glucose levels (4–6). Interestingly, it has recently been suggested that central and peripheral sensors appear to operate independently from one another as lesions that are made to PMV sensors do not influence the ability of central sensors to detect rapid-onset hypoglycemia but did prevent the detection of slow-onset hypoglycemia (7). This implies that these two sets of hypoglycemia sensors may exert differential roles in glucose sensation and glucose counterregulation and that they are not merely redundant mechanisms. Hypoglycemic signals from PMV glucose sensors that are transmitted to the central nervous system appear to use central pathways that are independent from those used by hypothalamic centers. Although much of our current understanding of glucose-sensing mechanisms stems from work that was conducted in the VMH of the brain (8), the existence of a relay circuit between PMV sensors, the brain, and the sympathoadrenal system has been postulated …