Exaggerated peripheral responses to catecholamines contributes to stress-induced hyperglycemia in the ob/ob mouse.
The present study investigated the contribution of altered sympathetic reactivity to the stress-induced hyperglycemia observed in the c57BL/6J (ob/ob) mouse, an animal model of type II diabetes. Blood glucose and insulin responses to sympathetic agonist and antagonist administration were evaluated in ob/ob mice and their nondiabetic, lean (ob/?) littermates. In addition, the ability of nutritional status to modify these responses was determined. These studies demonstrated that epinephrine administration to ob/ob mice caused an exaggerated increase in blood glucose and decrease in plasma insulin in ob/ob mice relative to lean littermates. The dose response curve for epinephrine-induced increases in blood glucose were shifted to the left, and the duration of the blood glucose and plasma insulin responses was longer. Differences between ob/ob mice and their nondiabetic littermates were greater when animals were tested in the fasted state. In addition, administration of the alpha adrenergic antagonist phentolamine caused a larger increase in plasma insulin in ob/ob mice than was observed in lean littermates. These results suggest that altered peripheral responses to sympathetic stimuli contribute to stress-induced hyperglycemia in ob/ob mice, and raise the possibility that altered sympathetic function is an etiologic factor in development of diabetes in these animals.
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology* / Q000502:physiology; D005215:Fasting; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008820:Mice, Obese; D009765:Obesity; D010646:Phentolamine / Q000494:pharmacology* / Q000502:physiology; D013312:Stress, Physiological / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D004837:Epinephrine; D010646:Phentolamine