Portal vein caffeine infusion enhances net hepatic glucose uptake during a glucose load in conscious dogs.
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.
Pencek
R Richard
RR
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. r.r.pencek@vanderbilt.edu
Battram
Danielle
D
Shearer
Jane
J
James
Freyja D
FD
Lacy
D Brooks
DB
Jabbour
Kareem
K
Williams
Phillip E
PE
Graham
Terry E
TE
Wasserman
David H
DH
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
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