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Department of Molecular Physiology & Biophysics and Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Arteriovenous difference and tracer
([3-3H]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 · min1
in eight dogs, at 10 and 20 pmol · kg1 · min1
in seven dogs, and at 0 pmol · kg1 · min1
in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol · kg1 · min1
[21.8 vs. 13.4 µmol · kg1 · min1
(control), P < 0.05]. Glucose utilization was
significantly increased during infusion at 10 and 20 pmol · kg1 · min1
[87.3 ± 8.3 and 105.3 ± 12.8, respectively, vs. 62.2 ± 5.3 and 74.7 ± 7.4 µmol · kg1 · min1
(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 · kg1 · min1
(22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol · kg1 · min1
(25 and 46% greater than control) and tended (P = 0.1)
to increase during GLP-1 infusion at 20 pmol · kg1 · min1
(24% greater than control). Intraportal infusion of GLP-1 at high
physiological and pharmacological rates increased glucose disposal
primarily in nonhepatic tissues.
incretin; net hepatic glucose uptake; muscle glucose uptake; blood glucose
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