The Response to Hypoglycemia: A Role for the Opioid System?

摘要

It is interesting to speculate how opioid action may modulate the counterregulatory response to acute hypo- glycemia. Glucose sensing during hypoglycemia occurs within specialized cells or neurons found in the central nervous system, predominantly in the hypothalamus and hindbrain, and the periphery (6). Most investigators in this field currently believe that recurrent hypoglycemia acts predominantly to alter glucose sensing within discrete hy- pothalamic regions such as the ventromedial hypothala- mus (VMH) (6). Recurrent hypoglycemia suppresses the counterregulatory response to 2-dexoyglucose-induced glucoprivation in the VMH (13) and reduces the sensitiv- ity of VMH glucose-sensing neurons to low glucose (14). Opioid receptors are expressed within the VMH and a number of other hypothalamic and thalamic regions where they might conceivably modulate glucose sensing during hypoglycemia (15). However, evidence for a direct role for opioids in the hypothalamus is limited to studies showing reversal of hypoglycemia-induced changes in gene expression (16), and there are as yet no in vivo animal studies that have examined the effect of hypothalamic ma- nipulation of opioid action on perturbations of glucose homeostasis such as hypoglycemia.