Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats.
To evaluate whether clonidine exerts its action within the central nervous system or outside the central nervous system to induce hyperglycemia, we compared the effects of clonidine injected into the third cerebral ventricle or intravenously on hepatic venous plasma glucose concentrations in fasted rats. Clonidine administration produced a dose-dependent hyperglycemia in each case. At all tested doses (5, 50, and 100 nmol) the hyperglycemic responses to clonidine injected intravenously were not significantly different from those to clonidine injected into the third cerebral ventricle. Intraperitoneal pretreatment with yohimbine (50 nmol) or phentolamine (50 nmol), both alpha-adrenergic antagonists, reduced the hyperglycemic response to clonidine (100 nmol) given intravenously, but these antagonists preinjected into the third cerebral ventricle did not reduce the response. Moreover, no significant differences in venous plasma clonidine concentrations were observed when intravenous and third cerebral ventricle injections of clonidine (100 nmol) were compared. These results suggest that clonidine-induced hyperglycemia is mainly mediated by the peripheral mechanism rather than through the central mechanism. To gain an insight into the peripheral mechanism for the hyperglycemic action of clonidine, we measured the plasma immunoreactive glucagon and insulin concentrations after intravenous clonidine (100 nmol). We found that plasma immunoreactive glucagon concentrations significantly increased, whereas plasma immunoreactive insulin concentrations did not change significantly despite hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D005215:Fasting; D005934:Glucagon / Q000097:blood; D006503:Hepatic Veins; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D015016:Yohimbine; D013004:Somatostatin; D005934:Glucagon; D003000:Clonidine; D010646:Phentolamine