title: Portal vein caffeine infusion enhances net hepatic glucose uptake during a glucose load in conscious dogs.
abstract: We determined whether intraportal caffeine infusion, at rates designed to create concentrations similar to that seen with normal dietary intake, would enhance net hepatic glucose uptake (NHGU) during a glucose load. Dogs (n = 15) were implanted with sampling and infusion catheters as well as flow probes >16 d before the studies. After a basal sampling period, dogs were administered a somatostatin infusion (0-150 min) as well as intraportal infusions of glucose [18 micromol/(kg . min)], basal glucagon [0.5 ng/(kg . min)], and insulin [8.3 pmol/(kg . min)] to establish mild hyperinsulinemia. Arterial glucose was clamped at 10 mmol/L with a peripheral glucose infusion. At 80 min, either saline (Control; n = 7) or caffeine [1.5 micromol/(kg . min); n = 8] was infused into the portal vein. Arterial insulin, glucagon, norepinephrine, and glucose did not differ between groups. In dogs infused with caffeine, NHGU was significantly higher than in controls [21.2 +/- 4.3 vs. 11.2 +/- 1.6 micromol/(kg . min)]. Caffeine increased net hepatic lactate output compared with controls [12.5 +/- 3.8 vs. 5.5 +/- 1.5 micromol/(kg . min)]. These findings indicate that physiologic circulating levels of caffeine can enhance NHGU during a glucose load, and the added glucose consumed by the liver is in part converted to lactate.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. r.r.pencek@vanderbilt.edu
authors.forename: R Richard
authors.initials: RR
authors.lastname: Pencek
authors.forename: Danielle
authors.initials: D
authors.lastname: Battram
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.forename: Freyja D
authors.initials: FD
authors.lastname: James
authors.forename: D Brooks
authors.initials: DB
authors.lastname: Lacy
authors.forename: Kareem
authors.initials: K
authors.lastname: Jabbour
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Williams
authors.forename: Terry E
authors.initials: TE
authors.lastname: Graham
authors.forename: David H
authors.initials: DH
authors.lastname: Wasserman
mesh_terms: D000409:Alanine / Q000097:blood; D000818:Animals; D001158:Arteries; D001786:Blood Glucose / Q000032:analysis; D002110:Caffeine / Q000008:administration & dosage*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005636:Fructosephosphates / Q000032:analysis; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism*; D015309:Glucose Clamp Technique; D019298:Glucose-6-Phosphate / Q000032:analysis; D005990:Glycerol / Q000097:blood; D006003:Glycogen / Q000032:analysis; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011169:Portal Vein
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005636:Fructosephosphates; D007328:Insulin; D019344:Lactic Acid; D002110:Caffeine; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D006003:Glycogen; D005934:Glucagon; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D009638:Norepinephrine; D004837:Epinephrine