Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo.
This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000032:analysis / Q000096:biosynthesis; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D013004:Somatostatin / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D019344:Lactic Acid; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose; D000409:Alanine