Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs.

In individuals with type 1 diabetes, hypoglycemia is a common consequence of overinsulinization. Under conditions of insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production. In contrast, during euglycemia, insulin potently inhibits glucagon's effect on the liver.

Islet auto-transplantation into an omental or splenic site results in a normal beta cell but abnormal alpha cell response to mild non-insulin-induced hypoglycemia.

The present studies were designed to determine if totally pancreatectomized dogs that underwent islet auto-transplantation retained a functional pancreatic counterregulatory response to mild non-insulin-induced hypoglycemia. Six dogs underwent total pancreatectomy followed by islet auto-transplantation to spleen or omentum. The animals recovered and fasting plasma glucose and insulin levels were normal.

Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal.

Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to peripheral glucose delivery. We hypothesize that the sympathetic nervous system normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two groups of 42-h-fasted conscious dogs were studied using arteriovenous difference techniques.

Insulin secretion-independent effects of GLP-1 on canine liver glucose metabolism do not involve portal vein GLP-1 receptors.

Whether glucagon-like peptide (GLP)-1 requires the hepatic portal vein to elicit its insulin secretion-independent effects on glucose disposal in vivo was assessed in conscious dogs using tracer and arteriovenous difference techniques. In study 1, six conscious overnight-fasted dogs underwent oral glucose tolerance testing (OGTT) to determine target GLP-1 concentrations during clamp studies. Peak arterial and portal values during OGTT ranged from 23 to 65 pM and from 46 to 113 pM, respectively.

Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia.

We evaluated the effect of chronic (3 wk) subcutaneous treatment with progesterone and estradiol (PE; producing serum levels observed in the 3rd trimester of pregnancy) or placebo (C) on hepatic and whole body insulin sensitivity and response to hypoglycemia in conscious, overnight-fasted nonpregnant female dogs, using tracer and arteriovenous difference techniques. Insulin was infused peripherally for 3 h at 1.8 mU x kg(-1) x min(-1).

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside causes acute hepatic insulin resistance in vivo.

The infusion of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) causes a rise in tissue concentrations of the AMP analog 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranotide (ZMP), which mimics an elevation of cellular AMP levels. The purpose of this work was to determine the effect of raising hepatic ZMP levels on hepatic insulin action in vivo. Dogs had sampling and infusion catheters as well as flow probes implanted 16 days before an experiment.

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.