Effect of centrally administered glucagon on liver glycogen & enzymes in anaesthetised dogs.

Glucagon (0.01 microgram) administered through the intracerebroventricular route in anaesthetised mongrel dogs, caused a significant rise in blood glucose and a fall in liver glycogen (P less than 0.01). Concurrently, it increased the liver phosphorylase, glutamic oxaloacetic transaminase, glutamic pyruvic transminase and lipase activities by 30 min. Identical changes were observed in vagotomised animals. In pancreatectomised animals as well as in spinal cord transectomised animals, glucagon did not cause these changes. The study indicated that the hyperglycaemia produced by the centrally administered glucagon, is possibly a result of liver glycogenolysis and gluconeogenesis induced by endogenous glucagon secreted from the pancreas, the stimulus for which is the hypothalamo-pancreatic fibres responding to glucagon sensitive neurones in the hypothalamus.

Effect of centrally administered glucagon on blood lipids in anesthetised dogs.

Previously we have proposed the existence of the central glucagon sensitive receptors in dogs. The present study was undertaken to explore the role of centrally administered glucagon on lipids in view of the proposed theory that the hypothalamic lipomobilizing centres are sensitive to glucose or substances that affect glucose metabolism. Glucagon (0.01 microgram) administered through the intracerebroventricular (ICV) route in anesthetised mongrel dogs, caused hypolipidemia (P greater than 0.001), hypocholesterolemia (P greater than 0.001), decreased blood free fatty acid (P greater than 0.001) and triglycerides (P greater than 0.001) levels; but increased blood high density lipoprotein (P greater than 0.01) level at 30 min. These effects on the central administration of glucagon, were not observed in pancreatectomised animals and spinal cord transectomised animals. Therefore, we conclude that the lipolysis on the central administration of glucagon, is caused by the endogenous glucagon secreted from the pancreas through the sympathetic fibers.

Effect of intracisternal injection of ACTH on blood glucose and hepatic glycogen in dogs.

The intracisternal administration of ACTH in a dose of 0.2 muU in mongrel dogs produced a significant (P less than 0.001) rise in blood glucose (BGL) and a fall (P less than 0.01) in hepatic glycogen concentration (HGC): in contrast its intravenous administration was devoid of this action. These changes were markedly reduced in the hepatic denervated animals and were completely abolished in animals with spinal cord transectomy. The above changes suggest that ACTH on the intracisternal administration causes a rise in the BGL by an action on the liver through the sympathetic fibers.

Effect of centrally administered glucagon on urinary sodium and potassium concentration in dogs.

The effects of glucagon administration through intracerebroventricular (ICV), third ventricular (TV) and intracisternal (I") routes on urinary sodium and potassium concentration have been studied in mongrel dogs. The central administration of glucagon resulted in a significant decrease in urinary sodium concentration (P less than 0.01) and increase in urinary potassium concentration (P less than 0.001). This change in urinary sodium and potassium concentration on central administration of glucagon was abolished in animals which were ventured to either sympathetic denervation or adrenalectomy. The observations in the present study suggest that the changes in urinary sodium and potassium concentration on central administration of glucagon, are due to increased secretion of some substance from the adrenals and the probable efferents might be the sympathetic fibres.

Effects of centrally administered insulin on urine output and sodium excretion in dogs.

The effects of insulin administration via intracerebroventricular (ICV), third ventricular (TV) and intracisternal (IC) routes on the urine output and sodium excretion have been studied in mongrel dogs. The central administration of insulin resulted in a significant increase in urine output and sodium excretion. This diuresis and natriuresis was not observed in animals which had undergone either spinal-cord transectomy or adrenalectomy. The insulin-sensitive receptors for this diuresis and natriuresis seem to be present in the vicinity of the fourth-ventricle of the brain. The observations in the present study suggest that the probable efferents might be the sympathetic fibers in the spinal-cord. The centrally administered insulin inhibits the secretion of some substance from the adrenal cortex, which in turn results in the diuresis and natriuresis in animals.

Effect of centrally administered insulin on blood glucose levels in dogs.

The effects of minimal doses of insulin administered by intracerebroventricular (ICV) and intracisternal (IC) routes in mongrel dogs, on peripheral blood glucose level (BGL) have been studied. The dose of 0.1 U of insulin was found to be the minimal dose. This dose produced an immediate short lived hyperglycaemia followed by a marked and sustained hypoglycaemia. Both the effects were not observed in spinal cord transected-vagosympathectomised animals. The immediate hyperglycaemic effect was not observed in adrenalectomised animals whereas the subsequent hypoglycaemic effect did not appear only when the liver was removed. In an attempt to identify the precise site of action in the central nervous system (CNS), The cerebellomedullary angles were found to be the most sensitive sites for the action of locally applied insulin. It is suggested that insulin on central administration causes a rise in the BGL by an action on the adrenal glands and subsequently causes a marked fall in BGL by an action on the liver through some nerve fibers.

Effect of centrally administered glucagon on urine output in dogs.

The effect of minimal doses of glucagon, administered by intracerebroventricular (ICV) and intracisternal(IC) routes, on urine output in mongrel dogs have been studied. The dose of 2.0 mug of glucagon was found to be the minimal dose for diuresis on peripheral administration. This dose when centrally administered, produced an oliguric effect in animals. This effect was not observed in vagosympathectomised-spinal cord transectomised or adrenalectomised animals. It is suggested that the probable efferents might be the sympathetic fibres as they are present in vagi nerves as well in the spinal cord (26). The observations made in an attempt to find out the organ responsible for the oliguric effect, showed that some substance released from the adrenal cortex has an influence on the kidney's excretory function.