CHRONIC EFFECTS OF INSULIN AND GLUCAGON UPON ISLET FUNCTION

Chronic administration of insulin to normal rats provokes a progressive reduction in both the pancreatic insulin content and the secretory responsiveness to glucose. The reduction of the secretory capacity is more marked than that of the stores of hormone. These results suggest that hyperinsulinism inhibits the secretory process within the beta-cell independently of its effects upon insulin synthesis. Prolonged treatment with zincglucagon also causes a reduction of the amount of insulin stored and secreted by the pancreas, but the ratio of insulin output to content is not significantly modified. The chronic influence of hyperglucagonism could thus correspond to a net catabolic effect upon the beta-cell. It is suggested that the reduced insulin-secretory capacity observed in experimental hyperinsulinism and hyperglucagonism could play a role in the impairment of glucose tolerance seen in the corresponding clinical conditions. © 1969 Springer-Verlag.