title: Indirect pathway of liver glycogen synthesis in humans is predominant and independent of beta-adrenergic mechanisms.
abstract: The relative contribution of the direct and indirect pathways to liver glycogen formation was assessed in humans by using a combined tracer-hepatic vein catheterization technique. An oral glucose load (75 g) labelled with 1-14C-glucose was administered to five subjects (control group) and 4.5 h later hepatic glycogen was flushed with glucagon and analysed to determine the randomization of 14C. The specific activity (SA) of the glycogen derived glucose (1-14C-glucose SA+recycled 14C-glucose SA) was 61 +/- 7% of the mean blood glucose SA of the interval 0-180 min after the oral glucose load. The relative values due to 1-14C-glucose and recycled 14C-glucose were 33 +/- 7 and 28 +/- 3%, respectively. The data indicate that the indirect pathway of glycogen formation is not only active in humans but contributes substantially (at least 50%) to liver glycogen formation. In order to investigate whether the basal adrenergic tone plays a role in the maintenance of the indirect pathway, the same protocol was also performed in a second group of subjects (n = 5) who received propranolol before the oral glucose load (propranolol group). The SA of the glycogen-derived glucose was considerably smaller than that of the control group (18 +/- 5 vs. 61 +/- 7%, P < 0.001), suggesting lesser glycogen formation. However, the ratio of 1-14C to recycled-14C in the glucose molecule was similar in the control (1.3 +/- 0.4) and propranolol group (1.9 +/- 1.2). We conclude that the basal adrenergic tone does not play any role in the operation of the indirect pathway of liver glycogen synthesis.
authors.affiliation: Department of Internal Medicine, Federico II University Second School of Medicine, Napoli, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Napoli
authors.forename: B
authors.initials: B
authors.lastname: Capaldo
authors.forename: A
authors.initials: A
authors.lastname: Picardi
authors.forename: F
authors.initials: F
authors.lastname: Piscione
authors.forename: M C
authors.initials: MC
authors.lastname: Bigazzi
authors.forename: C
authors.initials: C
authors.lastname: D'Ascia
authors.forename: L
authors.initials: L
authors.lastname: Saccà
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D008102:Liver Circulation; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D008112:Liver Glycogen; D011943:Receptors, Adrenergic, beta; D005934:Glucagon; D011433:Propranolol