title: Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion.
abstract: The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo. Liver glycogen levels were supercompensated (SCGly) in two groups (using intraportal fructose infusion) but not in two others (Gly) during hyperglycemic-normoinsulinemia. Following a 2-h control period during which fructose infusion was stopped, there was a 2-h experimental period in which the response to hyperglycemia plus either 4× basal insulin (INS) or portal vein glucose infusion (PoG) was measured. Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen (74 ± 3 vs. 53 ± 5% in Gly+INS and SCGly+INS, respectively, and 72 ± 3 vs. 50 ± 6% in Gly+PoG and SCGly+PoG, respectively). The reduction in liver glycogen synthesis in SCGly+INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly+PoG. These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. jason.winnick@vanderbilt.edu
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Winnick
authors.forename: Zhibo
authors.initials: Z
authors.lastname: An
authors.forename: Guillaume
authors.initials: G
authors.lastname: Kraft
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ramnanan
authors.forename: Jose M
authors.initials: JM
authors.lastname: Irimia
authors.forename: Marta
authors.initials: M
authors.lastname: Smith
authors.forename: Margaret
authors.initials: M
authors.lastname: Lautz
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roach
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005947:Glucose / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000096:biosynthesis*; D011169:Portal Vein / Q000378:metabolism
chemical_list: D008112:Liver Glycogen; D055372:AMP-Activated Protein Kinases; D005947:Glucose