Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade.
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.
Lekas
M C
MC
Departments of Physiology and Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Fisher
S J
SJ
El-Bahrani
B
B
van Delangeryt
M
M
Vranic
M
M
Shi
Z Q
ZQ
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*
D018663:Adrenergic Agents; D001786:Blood Glucose; D002395:Catecholamines; D005227:Fatty Acids; D007328:Insulin; D019344:Lactic Acid; D002217:Carbachol; D005934:Glucagon; D005947:Glucose; D010646:Phentolamine