Minireview: The value of looking backward: the essential role of the hindbrain in counterregulatory responses to glucose deficit.

This review focuses on evidence indicating a key role for the hindbrain in mobilizing behavioral, autonomic and endocrine counterregulatory responses to acute and profound glucose deficit, and identifies hindbrain norepinephrine (NE) and epinephrine (E) neurons as essential mediators of some of these responses. It has become clear that hindbrain NE/E neurons are functionally diverse. However, considerable progress has been made in identifying the particular NE/E neurons important for particular glucoregulatory responses. Although it is not yet known whether NE/E neurons are directly activated by glucose deficit, compelling evidence indicates that if they are not, the primary glucoreceptor cells must be located in the immediate vicinity these neurons. Hindbrain studies identifying cellular markers associated with glucose-sensing functions in other brain regions are discussed, as are studies examining the relationship of these markers to counterregulatory responses of NE/E neurons. Further investigations to identify glucose-sensing cells (neurons, ependymocytes, or glia) controlling counterregulatory responses are crucial, as are studies to determine the specific functions of glucose-sensing cells throughout the brain. Likewise, examination of the roles (if any) of hindbrain counterregulatory systems in managing glucose homeostasis under basal, nonglucoprivic conditions will also be important for a full understanding of energy homeostasis. Nevertheless, the accumulated evidence demonstrates that hindbrain glucose sensors and NE/E neurons are essential players in triggering counterregulatory responses to emergencies of glucose deficit.