Intraportal GLP-1 infusion increases nonhepatic glucose utilization without changing pancreatic hormone levels.
After a meal, glucagon-like peptide-1 (GLP-1) levels in the hepatic portal vein are elevated and are twice those in peripheral blood. The aim of this study was to determine whether any of GLP-1's acute metabolic effects are initiated within the hepatic portal vein. Experiments consisted of a 40-min basal period, followed by a 240-min experimental period, during which conscious 42-h-fasted dogs received glucose intraportally (4 mgxkg(-1)xmin(-1)) and peripherally (as needed) to maintain arterial plasma glucose levels at approximately 160 mg/dl. In addition, saline was given intraportally (CON; n = 8) or GLP-1 (1 pmolxkg(-1)xmin(-1)) was given into the hepatic portal vein (POR; n = 11) or the hepatic artery (HAT; n = 8). Portal vein plasma GLP-1 levels were basal in CON, 20x basal in POR, and 10x basal in HAT, whereas levels in the periphery and liver were the same in HAT and CON. The glucose infusion rate required to maintain hyperglycemia was significantly greater in POR (8.5 +/- 0.7 mgxkg(-1)xmin(-1), final 2 h) than in either CON or HAT (6.0 +/- 0.5 or 6.7 +/- 1.0 mgxkg(-1)xmin(-1), respectively). There were no differences among groups in either arterial plasma insulin (24 +/- 2, 23 +/- 3, and 23 +/- 3 microU/ml for CON, POR, and HAT, respectively) or glucagon (23 +/- 2, 30 +/- 3, and 25 +/- 2 pg/ml) levels during the experimental period. The increased need for glucose infusion reflected greater nonhepatic as opposed to liver glucose uptake. GLP-1 infusion increased glucose disposal independently of changes in pancreatic hormone secretion but only when the peptide was delivered intraportally.
Johnson
Kathryn M S
KM
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, 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 / Q000032:analysis; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010187:Pancreatic Hormones / Q000378:metabolism*; D011169:Portal Vein; D012039:Regional Blood Flow
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010187:Pancreatic Hormones; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose