Intraportally delivered GLP-1, in the presence of hyperglycemia induced via peripheral glucose infusion, does not change whole body glucose utilization.
After a meal, glucagon-like peptide-1 (GLP-1) and glucose levels are significantly greater in the hepatic portal vein than in the artery. We have previously reported that, in the presence of intraportal glucose delivery, a physiological increase of GLP-1 in the hepatic portal vein increases nonhepatic glucose uptake via a mechanism independent of changes in pancreatic hormone secretion. The aim of the present study was to determine whether intraportal glucose delivery is required to observe this effect. Experiments consisted of a 40-min basal period, followed by a 240-min experimental period, during which conscious 42-h fasted dogs received glucose peripherally to maintain arterial plasma glucose levels at approximately 160 mg/dl. In addition, either saline (n = 6) or GLP-1 (1 pmol.kg(-1).min(-1); GLP-1, n = 6) was administered intraportally during the experimental period. As in the previous study, the presence of GLP-1 did not alter pancreatic hormone levels; however, in the present study, intraportal GLP-1 infusion did not result in an increase in whole body glucose utilization. This is despite the fact that arterial and hepatic portal vein GLP-1 levels were maintained at the same level as the previous study. Therefore, a physiological elevation of GLP-1 in the hepatic portal vein does not increase whole body glucose uptake when hyperglycemia is induced by peripheral glucose infusion. This indicates that a physiological increase in GLP-1 augments glucose utilization only when GLP-1 and glucose gradients conditions mimic the postprandial state.
Johnson
Kathryn M S
KM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA. kathryn.johnson@vanderbilt.edu
Edgerton
Dale S
DS
Rodewald
Tiffany
T
Scott
Melanie
M
Farmer
Ben
B
Neal
Doss
D
Cherrington
Alan D
AD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects; D008297:Male
D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose