Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs

Arteriovenous difference and tracer ([3-H-3] 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 mumol.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 mu mol.g(-1).mn(-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.g(-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.