title: Inability of hyperglycemia to counter the ability of glucagon to increase net glucose output and activate glycogen phosphorylase in the perfused rat liver.
abstract: We examined the ability of hyperglycemia to alter the ability of glucagon to activate phosphorylase and stimulate glucose output in perfused rat livers. The livers were perfused with a Krebs-Henseleit buffer containing washed bovine erythrocytes and albumin at 37 degrees C for 90 or 120 minutes, In the first 60 minutes, the livers were perfused with insulin (10 microU/mL), glucagon (11 pg/mL), and glucose (105, 230, or 440 mg/dL). In the second 30 or 60 minutes, the glucagon concentration in the perfusate was elevated to 44, 88, 176 or 352 pg/mL or the infusion of glucagon was terminated. In the presence of glucose at 105 mg/dL, the termination of glucagon infusion decreased phosphorylase activity and glucose output. In contrast, the elevation of glucagon from 11 to 352 pg/mL activated phosphorylase and increased net glucose output in a dose-dependent manner. A linear correlation was observed between net glucose output and glycogen phosphorylase activity. An elevation of the glucose concentration from 105 to 230 or 440 mg/dL decreased net glucose output from 0.81 +/- 0.03 to 0.66 +/- 0.09 or -0.004 +/- 0.21 mg/min/100 g body weight, respectively, but did not cause significant change in phosphorylase-a activity (105 mg/dl, 50 +/- 11; 230 mg/dL, 40 +/- 2; 440 mg/dL, 69 +/ 3 mU/mg protein). The elevation of the glucagon concentration from 11 to 88 microU/mL in the presence of glucose at 105, 230, or 440 mg/dL increased net glucose output by 0.65 +/- 0.06, 0.61 +/- 0.08 or 0.64 +/- 0.26 mg/min 100 g body weight and raised phosphorylase-a activity by 65 +/- 5, 82 +/- 11, or 55 +/- 4 mU/mg protein, respectively. These results suggest that hyperglycemia decreases net hepatic glucose output without changing the activity of phosphory-lase-a. Further hyperglycemia does not alter the ability of glucagon to activate phosphorylase or to stimulate net hepatic glucose output.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shiota
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.forename: C A
authors.initials: CA
authors.lastname: Colburn
authors.forename: G
authors.initials: G
authors.lastname: Mitchell
authors.forename: A D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D006005:Phosphorylases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D006005:Phosphorylases; D005947:Glucose