Hyperinsulinemia in rats with hypothalamic obesity: effects of autonomic drugs and glucose.
The present study examined the effects of autonomic drugs and glucose on the insulin and glucose concentrations of sham-operated rats and of rats with ventromedial hypothalamic (VMH) lesions and obesity. In the basal condition both epinephrine and atropine significantly decreased serum insulin levels in VMH-lesioned but not sham-operated rats. During glucose stimulation of insulin secretion in VMH-lesioned rats, epinephrine inhibited the increase of insulin by 83% and atropine inhibited it by 42%; whereas in sham-operated rats, epinephrine inhibited it by 70% and atropine inhibited it by 34%. Epinephrine with atropine completely blocked the increase of insulin in response to glucose in both VMH-lesioned and sham-operated rats. In the basal condition, epinephrine together with propranolol significantly decreased serum insulin levels in VMH-lesioned but not sham-operated rats. Epinephrine with phentolamine, on the other hand, markedly increased insulin in the VMH-lesioned rats and to a lesser degree in the sham-operated rats. During glucose stimulation epinephrine with propranolol inhibited the increase of insulin in both groups. Epinephrine with phentolamine or isoproterenol markedly increased serum insulin in VMH-lesioned rats. These results suggest that stimulation of the vagus nerve and increased sensitivity of the beta-receptors on the beta-cells of the islet contribute to the development of hyperinsulinemia. The sympathetic contribution may also be through suppression of alpha-adrenergic receptors.
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006946:Hyperinsulinism / Q000150:complications / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D010646:Phentolamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*
D001285:Atropine; D011433:Propranolol; D005947:Glucose; D007545:Isoproterenol; D004837:Epinephrine; D010646:Phentolamine