Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs.
Arteriovenous difference and tracer ([3-(3)H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7-36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol. kg(-1). min(-1) in eight dogs, at 10 and 20 pmol. kg(-1). min(-1) in seven dogs, and at 0 pmol. kg(-1). min(-1) in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol. kg(-1). min(-1) [21.8 vs. 13.4 micromol. kg(-1). min(-1) (control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol. kg(-1). min(-1) [87.3 +/- 8.3 and 105.3 +/- 12.8, respectively, vs. 62.2 +/- 5.3 and 74.7 +/- 7.4 micromol. kg(-1). min(-1) (control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased (P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol. kg(-1). min(-1) (22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol. kg(-1). min(-1) (25 and 46% greater than control) and tended (P = 0.1) to increase during GLP-1 infusion at 20 pmol. kg(-1). min(-1) (24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.
Nishizawa
Makoto
M
Department of Molecular Physiology & Biophysics, Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Moore
Mary Courtney
MC
Shiota
Masakazu
M
Gustavson
Stephanie M
SM
Snead
Wanda L
WL
Neal
Doss W
DW
Cherrington
Alan D
AD
D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002319:Cardiovascular System / Q000187:drug effects; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000008:administration & dosage*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D006003:Glycogen / Q000096:biosynthesis; D006728:Hormones / Q000097:blood; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000008:administration & dosage*; D011169:Portal Vein; D011498:Protein Precursors / Q000008:administration & dosage*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D019344:Lactic Acid; D052216:Glucagon-Like Peptide 1; D006003:Glycogen; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol