Heterogeneity of plasma glucagon immunoreactivity in normal, depancreatized, and alloxan-diabetic dogs

Abstract

Filtration of basal plasma from normal, alloxan-diabetic, and depancreatized dogs on Bio Gel P-10 yielded four glucagon-immunoreactive fractions. One of them appeared in the true glucagon area with the glucagon- 125I (3500 mol wt). Of the other three, one appeared in the void volume (>20000 mol wt), another just before the insulin- 125I (⋍9000 mol wt), and the last one close to the salt peak (<2000 mol wt). The increase of total plasma glucagon immunoreactivity observed in depancreatized and alloxan diabetic dogs was mainly due to an increase in the 3500 and 9000 molecular-weight fractions. Arginine infusion in depancreatized dogs caused an increase in the 3500 molecular-weight fraction. Somatostatin or insulin infusion in depancreatized and alloxan-diabetic dogs resulted in disappearance of the 3500 molecular-weight fraction. In a hypoglycemic phloridzinized dog, the marked hyperglucagonemia observed was due to an increase in the 3500 and 9000 molecular-weight fractions; suppression by somatostatin infusion resulted in disappearance of the 3500 molecular-weight fraction and a marked reduction of the 9000 molecular-weight fraction. The high levels of 9000 molecular-weight fraction in the hyperglucagonemic dogs could represent increased entry of glucagon precursors into the circulation. Postpancreatectomy plasma glucagon does not seem to differ qualitatively from plasma glucagon secreted by the A cells in the intact animal, since the patterns of glucagon immunoreactivity in depancreatized dogs and in normal and alloxandiabetic dogs are similar.