title: Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade.
abstract: Glucose utilization increases markedly in the normal dog during stress induced by the intracerebroventricular (ICV) injection of carbachol. To determine the extent to which insulin, glucagon, and selective (alpha/beta)-adrenergic activation mediate the increment in glucose metabolic clearance rate (MCR) and glucose production (R(a)), we used five groups of normal mongrel dogs: 1) pancreatic clamp (PC; n = 7) with peripheral somatostatin (0.8 microg x kg(-1) x min(-1)) and intraportal replacement of insulin (1,482 +/- 84 pmol x kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)) infusions; 2) PC plus combined alpha (phentolamine)- and beta (propranolol)-blockade (7 and 5 microg x kg(-1) x min(-1), respectively; alpha+beta; n = 5); 3) PC plus alpha-blockade (alpha; n = 6); 4) PC plus beta-blockade (beta; n = 5); and 5) a carbachol control group without PC (Con; n = 10). During ICV carbachol stress (0-120 min), catecholamines, ACTH, and cortisol increased in all groups. Baseline insulin and glucagon levels were maintained in all groups except Con, where glucagon rose 33%, and alpha, where insulin increased slightly but significantly. Stress increased (P < 0.05) plasma glucose in Con, PC, and alpha but decreased it in beta and alpha+beta. The MCR increment was greater (P < 0.05) in beta and alpha+beta than in Con, PC, and alpha. R(a) increased (P < 0.05) in all groups but was attenuated in alpha+beta. Stress-induced lipolysis was abolished in beta (P < 0.05). The marked rise in lactate in Con, PC, and alpha was abolished in alpha+beta and beta. We conclude that the stress-induced increase in MCR is largely independent of changes in insulin, markedly augmented by beta-blockade, and related, at least in part, to inhibition of lipolysis and glycogenolysis, and that R(a) is augmented by glucagon and alpha- and beta-catecholamine effects.
authors.affiliation: Departments of Physiology and Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: M C
authors.initials: MC
authors.lastname: Lekas
authors.forename: S J
authors.initials: SJ
authors.lastname: Fisher
authors.forename: B
authors.initials: B
authors.lastname: El-Bahrani
authors.forename: M
authors.initials: M
authors.lastname: van Delangeryt
authors.forename: M
authors.initials: M
authors.lastname: Vranic
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Shi
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol; D002395:Catecholamines / Q000097:blood; D002552:Cerebral Ventricles; D004285:Dogs; D005227:Fatty Acids / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008026:Ligation; D008297:Male; D008657:Metabolic Clearance Rate; D010179:Pancreas / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D001786:Blood Glucose; D002395:Catecholamines; D005227:Fatty Acids; D007328:Insulin; D019344:Lactic Acid; D002217:Carbachol; D005934:Glucagon; D005947:Glucose; D010646:Phentolamine