Vagotomy or atropine blocks hypoglycemic effect of insulin injected into ventromedial hypothalamic nucleus.

Stereotaxic microinjections of insulin (100 microU) into the ventromedial hypothalamic nucleus (VMN) resulted in rapid decrease, whereas injection of control saline into the same region caused a slight increase of hepatic venous plasma glucose concentration in rats. The hypoglycemic effect of insulin injected into the VMN was eliminated by pretreatment of the animals with atropine but not with propranolol or with phentolamine. Subdiaphragmatic vagotomy also prevented the decrease of hepatic venous plasma glucose concentration seen after microinjection of insulin into the VMN. These results support the hypothesis that the VMN is an insulin-sensitive glucoregulator center or that it is part of one and that the glucoregulatory impulse that originates in the VMN reaches the effector organ, the liver, through the cholinergic fibers of the vagus nerves.

Decrease in plasma glucose concentration after microinjection of insulin into VMN.

The influence of insulin on hypothalamic regulation of blood sugar homeostatis was studied in anesthetized rats. Insulin was injected directly into the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area (LHA), the parietal cortex, or the third cerebral ventricle, and changes in hepatic venous plasma glucose concentrations were studied. After injection of 100 microU insulin into the parietal cortex or the third ventricle, hepatic venous plasma glucose concentration did not differ from that of the control rats, which received saline injection into the same CNS regions. Saline injection into the LHA raised the hepatic venous plasma glucose concentration in control rats, where injection of 100 microU insulin into the LHA resulted in a modest but significant decrease of glycemia in the 2-, 5-, and 10-min postinjection samples. As little as 10 microU insulin injected into the VMN eliminated the hyperglycemic response seen in control rats after saline injection into this site. The divergence between insulin-treated rats and their saline-treated controls was further amplified, and an actual fall of plasma glucose was observed in rats given injections of 50 or 100 microU insulin into the VMN. Increasing quantities of insulin (from 10 to 100 microU) injected into the VMN resulted in graded decreases of hepatic venous plasma glucose concentrations, suggestive of a dose-response curve. These observations support the hypothesis that the VMN and the LHA are parts of an insulin-sensitive CNS glucoregulator system that exerts influences on the systemic blood glucose levels by causing rapid alterations in hepatic glucose metabolism.

Transjugular hepatic vein cannulation in rats with nonisotopic in vivo verification.

A simple, rapid and relatively atraumatic method for transjugular cannulation of the hepatic vein and for repeated sampling of hepatic venous blood in the rat is described. Preliminary in vivo verification of the cannula's position is proposed, either by using the glucose differential between consecutive samples of the hepatic venous blood and inferior vena cava blood, or more practically, by using the glucose differential between the hepatic venous blood and tail blood obtained simultaneously. The latter procedure is favored because of its technical simplicity.