title: Direct and indirect effects of insulin on glucose uptake and storage by the liver.
abstract: Studies were conducted in conscious 42-h-fasted dogs to determine how much of insulin's effect on hepatic glucose uptake arises from its direct hepatic action versus its indirect (extrahepatic) action. Each experiment consisted of equilibration, basal, and experimental periods. During the latter, somatostatin, basal intraportal glucagon, portal glucose (21.3 micromol x kg(-1) x min(-1)), and peripheral glucose (to double the hepatic glucose load) were infused. During the experimental period, insulin was infused intraportally at a basal rate (BI, n = 6), at a fourfold basal rate (PoI, n = 6), or via a peripheral vein to create a selective increase in the arterial insulin level similar to that in PoI (PeI, n = 6). Arterial and hepatic sinusoidal insulin levels (in picomoles per liter) during the experimental period were 31 +/- 5 and 113 +/- 15 in BI, 97 +/- 11 and 394 +/- 66 in PoI, and 111 +/- 13 and 96 +/- 9 in PeI, respectively. Net hepatic glucose uptake (NHGU) averaged 7.0 +/- 1.1 micromol x kg(-1) x min(-1), 15.7 +/- 2.7 micromol x kg(-1) x min(-1) (P < 0.05 vs. BI), and 12.0 +/- 2.4 micromol x kg(-1) x min(-1) (P < 0.05 vs. BI) in BI, PoI, and PeI, respectively. Net hepatic carbon retention was 4.4 +/- 1.2 micromol glucose equivalents. kg(-1) x min(-1), 12.3 +/- 2.5 micromol glucose equivalents x kg(-1) x min(-1) (P < 0.05 vs. BI, P < 0.05 vs. PeI), and 7.1 +/- 1.0 micromol glucose equivalents x kg(-1) x min(-1) (P < 0.05 vs. BI) in BI, PoI, and PeI, respectively. Both direct and indirect insulin actions increase NHGU, but the rise in hepatic sinusoidal insulin appears critical for efficient storage of glucose as hepatic glycogen.
authors.affiliation: Department of Molecular Physiology and Biophysics, and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Shosuke
authors.initials: S
authors.lastname: Satake
authors.forename: Mary Courtney
authors.initials: MC
authors.lastname: Moore
authors.forename: Kayano
authors.initials: K
authors.lastname: Igawa
authors.forename: Margaret
authors.initials: M
authors.lastname: Converse
authors.forename: Benjamin
authors.initials: B
authors.lastname: Farmer
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001158:Arteries; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D004285:Dogs; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011169:Portal Vein; D013004:Somatostatin / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D002245:Carbon Dioxide; D019344:Lactic Acid; D013004:Somatostatin; D006003:Glycogen; D005934:Glucagon; D005947:Glucose; D005990:Glycerol