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1 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
2 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA; Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN, USA
3 Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: genie.moore{at}vanderbilt.edu.
Arteriovenous difference and tracer ([3-3H]glucose) techniques were used in 42h-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 8 dogs, 10 and 20 pmol.kg-1.min-1 in 7 dogs, and 0 pmol.kg-1.min-1 in 8 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 µmol.kg-1.min-1 [Control], P<0.05). Glucose Rd was significantly increased during infusion of 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 µmol.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-physiologic and pharmacologic rates increased glucose disposal primarily in nonhepatic tissues.
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