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 (α/β)- 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 μg · kg^-1 · min^-1) and intraportal replacement of insulin (1,482 ± 84 pmol · kg^-1 · min^-1) and glucagon (0.65 ng · kg^-1 · min^-1) infusions; 2) PC plus combined α (phentolamine)- and β (propranolol)- blockade (7 and 5 μg · kg^-1 · min^-1, respectively; α+β; n = 5); 3) PC plus α-blockade (α; n = 6); 4) PC plus β-blockade (β; 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 α, where insulin increased slightly but significantly. Stress increased (P < 0.05) plasma glucose in Con, PC, and but decreased it in β and α+β. The MCR increment was greater (P < 0.05) in β and α+β than in Con, PC, and α. R(a) increased (P < 0.05) in all groups but was attenuated in α+β. Stress-induced lipolysis was abolished in β (P < 0.05). The marked rise in lactate in Con, PC, and α was abolished in α+β and β. We conclude that the stress-induced increase in MCR is largely independent of changes in insulin, markedly augmented by β-blockade, and related, at least in part, to inhibition of lipolysis and glycogenolysis, and that R(a) is augmented by glucagon and α- and β-catecholamine effects.