Abstract
In the present study the role of glucagon in normal physiology was re-examined. Neutralisation of endogenous glucagon by glucagon antibodies was used as a tool in unravelling glucagon's role in glucose homeostasis. Glucagon did not prove to be that important for the maintenance of basal blood glucose levels in fasting rats. Its contribution in the recovery from insulin-induced hypoglycaemia was not found principal among other counter-regulatory hormones. However, its direct insulinotropic activity was substantiated. Rats given exogenous glucagon antibodies with very high affinity and binding capacity and rabbits immunised against glucagon showed impaired insulin response to arginine stimulation. From the conducted studies, there is evidence that glucagon antibodies can enter into the interstitial space of the pancreatic islets and block the paracrine effects that glucagon exerts on the cells of different type that exist in the endocrine pancreas. The effect of L-tryptophan on A-cells of the pancreas was studied after oral and intravenous administration of this amino acid. The different pattern of glucagon response obtained could be attributed to the glucagonotropic activity of gastric inhibitory polypeptide (GIP), implicating an important role of glucagon in the enteroinsular axis. The effect of adrenaline and somatostatin on the stimulation of insulin and glucagon by L-tryptophan was also studied. The inhibitory action of somatostatin on A- and B-cells of the pancreas was confirmed as well as the inhibitory action of adrenaline only on B-cells. Finally, an immunoassay for total, glucagon-like immuno-reactivity was developed. Gut glucagon-like immunoreactivity was measured after two different meals with and without addition of guar gum in normal and diabetic subjects. The results could not exclude the possible role of gut glucagon-like immunoreactants as a mediator of enteroinsular axis.