Hepatic alpha- and beta-adrenergic receptors are not essential for the increase in R-a during exercise in diabetes

The purpose of this study was to determine the role of direct hepatic adren ergic stimulation in the control of endogenous glucose production (R-a) dur ing moderate exercise in poorly controlled alloxan-diabetic dogs. Chronical ly catheterized and instrumented (flow probes on hepatic artery and portal vein) dogs were made diabetic by administration of alloxan. Each study cons isted of a 120-min equilibration, 30-min basal, 150-min moderate exercise, 30-min recovery, and 30-min blockade test period. Either vehicle (control; n = 6) or a (phentolamine)- and beta (propranolol)-adrenergic blockers (HAB ; n = 6) were infused in the portal vein. In both groups, epinephrine (Epi) and norepinephrine (NE) were infused in the portal vein during the blockad e test period to create suprapharmacological levels at the liver. Isotopic ([3-H-3]glucose, [U-C-14]alanine) and arteriovenous difference methods were used to assess hepatic function. Arterial plasma glucose was similar in co ntrols (345 +/- 24 mg/dl) and HAB (336 +/- 23 mg/dl) and was unchanged by e xercise. Basal arterial insulin was 5 +/- 1 mU/ml in controls and 4 +/- 1 m U/ml in HAB and fell by similar to 50% during exercise in both groups. Basa l arterial glucagon was similar in controls (56 +/- 10 pg/ml) and HAB (55 /- 7 pg/ml) and rose similarly, by similar to 1.4-fold, with exercise in bo th groups. Despite greater arterial Epi and NE levels in HAB compared with controls during the basal and exercise periods, exercise-induced increases in catecholamines from basal were similar in both groups. Gluconeogenic con version from alanine and lactate and the intrahepatic efficiency of this pr ocess were increased by twofold during exercise in both groups. R-a rose si milarly by 2.9 +/- 0.7 and 2.7 +/- 1.0 mg.kg(-1).min(-1) at time = 150 min during exercise in controls and HAB. During the blockade test period, arter ial plasma glucose and R-a rose to 454 +/- 43 mg/dl and 11.3 mg.kg(-1).min( -1) in controls, respectively, but were essentially unchanged in HAB. The a ttenuated response to the blockade test in HAB substantiates the effectiven ess of the hepatic adrenergic blockade. In conclusion, these results demons trate that direct hepatic adrenergic stimulation does not play a role in th e stimulation of R-a during exercise in poorly controlled diabetes.