Hypoglycemic Detection at the Portal Vein

Absent in Humans or Yet to Be Elucidated?

With the advent of more intensive glucose management, hypoglycemia has emerged as a primary limitation in the treatment of insulin-dependent diabetes. It is now recognized that the increased incidence of hypoglycemia derives not only from imperfect insulin replacement but also from impaired counterregulation and hypoglycemic unawareness (1). The latter two observations have led to a renewed interest in the mechanisms underlying hypoglycemic detection. As a result of intensive research over the past decade, the traditional hypothalamocentric model of glucose sensing has been replaced with one emphasizing a widespread neural network involving numerous aspects of the central nervous system, as well as peripheral sensory input. Thus, in addition to the ventromedial hypothalamus, the paraventricular hypothalamus, arcuate nucleus, area postrema, nucleus of the solitary tract, and dorsal motor nucleus all appear to play important roles (2,3). In the periphery, important glucose sensors have been identified in the carotid bodies (4), gastrointestinal tract (5), and portal-mesenteric vein (6). For hypoglycemic detection, the glucose sensors of the portal-mesenteric vein have garnered the most attention. Animal studies have repeatedly demonstrated that blocking portal glucose sensing via portal glucose infusion (7) or denervating the portal vein (8) substantially suppresses the sympathoadrenal response to hypoglycemia. More recently, it was shown that portal-mesenteric vein glucose sensing is particularly important when hypoglycemia develops slowly and, under these conditions, modulates over 90% of the sympathoadrenal response to hypoglycemia (9).

While portal …