Portal infusion of escitalopram enhances hepatic glucose disposal in conscious dogs.

To examine whether escitalopram enhances net hepatic glucose uptake during a hyperinsulinemic hyperglycemic clamp, studies were performed in conscious 42-h-fasted dogs. The experimental period was divided into P1 (0-90 min) and P2 (90-270 min). During P1 and P2 somatostatin (to inhibit insulin and glucagon secretion), 4x basal intraportal insulin, basal intraportal glucagon, and peripheral glucose (2x hepatic glucose load) were infused.

Hepatic portal venous delivery of a nitric oxide synthase inhibitor enhances net hepatic glucose uptake.

Hepatic portal venous infusion of nitric oxide synthase (NOS) inhibitors causes muscle insulin resistance, but the effects on hepatic glucose disposition are unknown. Conscious dogs underwent a hyperinsulinemic (4-fold basal) hyperglycemic (hepatic glucose load 2-fold basal) clamp, with assessment of liver metabolism by arteriovenous difference methods. After 90 min (P1), dogs were divided into two groups: control (receiving intraportal saline infusion; n = 8) and LN [receiving N(G)-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor; n = 11] intraportally at 0.

Intraportally delivered GLP-1, in the presence of hyperglycemia induced via peripheral glucose infusion, does not change whole body glucose utilization.

After a meal, glucagon-like peptide-1 (GLP-1) and glucose levels are significantly greater in the hepatic portal vein than in the artery. We have previously reported that, in the presence of intraportal glucose delivery, a physiological increase of GLP-1 in the hepatic portal vein increases nonhepatic glucose uptake via a mechanism independent of changes in pancreatic hormone secretion. The aim of the present study was to determine whether intraportal glucose delivery is required to observe this effect.

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.

A novel glucagon receptor antagonist, NNC 25-0926, blunts hepatic glucose production in the conscious dog.

Elevated glucagon is associated with fasting hyperglycemia in type 2 diabetes. We assessed the effects of the glucagon receptor antagonist (2R)-N-[4-({4-(1-cyclohexen-1-yl)[(3,5-dichloroanilino)carbonyl]anilino}methyl)benzoyl]-2-hydroxy-b-alanine (NNC 25-0926) on hepatic glucose production (HPG) in vivo, using arteriovenous difference and tracer techniques in conscious dogs. The experiments consisted of equilibration (-140 to -40 min), control (40-0 min), and experimental [0-180 min, divided into P1 (0-60 min) and P2 (60-180 min)] periods.