Adrenoceptor-mediated control of glucose homeostasis in obese hyperglycaemic (ob/ob) mice

Adrenoceptor-mediated control of glucose homeostasis in lean (+/+) and obese hyperglycaemic (ob/ob) mice was investigated by intraperitoneal administration of alpha and beta adrenoceptor agonists and antagonists, and by chemical sympathectomy. In lean mice, beta adrenoceptor stimulation with isoprenaline (50 mumol/kg) transiently raised plasma insulin and lowered plasma glucose, while alpha adrenoceptor stimulation with phenylephrine (50 mumol/kg) transiently lowered plasma insulin and raised plasma glucose. In ob/ob mice the insulin responses to isoprenaline and phenylephrine were similar but more slowly generated and protracted. However in contrast to lean mice, isoprenaline transiently raised plasma glucose and phenylephrine lowered plasma glucose in ob/ob mice. Beta adrenoceptor antagonism with propranolol (100 mumol/kg) produced a more protracted decrease of plasma insulin in ob/ob mice than lean mice, although plasma glucose was not significantly altered in either genotype. Alpha adrenoceptor antagonism with phentolamine (100 mumol/kg) transiently increased plasma insulin and produced a protracted decrease of plasma glucose in both genotypes. Chemical sympathectomy with 6-hydroxydopamine (65 mg/kg ip) temporarily reduced food intake and plasma glucose without affecting plasma insulin in lean mice. In ob/ob mice, chemical sympathectomy produced temporary but marked reductions of food and fluid intake with concomitant reductions in plasma glucose and insulin. Plasma glucose and insulin returned almost to pretreatment values by 7 days, whereas fluid intake rose to above pretreatment amounts and food intake became maintained at the amount consumed by lean mice. Food and fluid intake returned to pretreatment amounts at 4-5 weeks. The results indicate abnormalities of adrenoceptor mechanisms in ob/ob mice which favour impaired glucose homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)