Histological studies on the islets of Langerhans in normal rabbits and rats and those treated with sulfonamide derivatives.

As Janbon first reported in 1942, some sulfonamide derivatives(S)have an action which lowers blood sugar level, and they are nowadays profited to clinical practice. There are several opinions in regard to the mechanism of the hypoglycemic action of S, such as, increased secretion of insulin or inhibition of the discharge of glucagon, etc. , however, it has not yet been completely understood. It is reported that degeneration or disapearance of the alpha cells in the islets of Langerhans is observed after the administration of S(Holt, 1955;Ferner, 1957), and it is also known that it has a strong destructive action on rats which is the same as that of synthalin A. Yoshioka(1956)reported that he observed a decrease in the number of alpha cells associated with a release of alpha-granules in rabbits after injection of BZ-55. Therefore it was considered that the hypoglycemia which occured in this case might have been based on the inhibition of glucagon secretion. However, there are many reports emphasizing that the change in the islets of Langerhans occurs not only in alpha cells but also in beta cells. Heinivaara(1956), Schmide and Blobel(1956), Ashworth and Haist(1956) suggested that the effect of these preparations on the islets of Langerhans varies with the dosage and that these preparations do not act selectively on alpha cells. Gepts et al. (1956) stated that the hypoglycemic effect of S is not due to the damage of alpha cells but to the stimulation of beta cells followed by an excess release of insulin. They also stated that the persistent administration of S to rats led to a proliferous change in the islets of Langerhans and that from the numerous beta cells a large amount of insulin is secreted. On the other hand the administration of S could not induce hypoglycemia in alloxan diabetic rats; from this fact it was presumed that the release of insulin could not be carried out owing to impairment of the beta cells. However, Mirsky et al. (1957)have reported that these preparations are effective in chickens treated with alloxan and pancreatectomized ducks. Thus modern considerations for the hypoglycemic action of S are favorable to the classical beta cell theory by Loubatieres (1944), who recently reported(1955)that IPTD stimulates both alpha and beta cells to accelerate the secretion of glucagon and insulin, but the delicate efficiency of the former is always shaded by the strong action of the latter, with consequent result of the occurence of hypoglycemia. In spite of many announcements con-