[Historical review of insulin and its preparations in pharmacopoeia (3). Fish insulins].

Existence of encapsulated glands situated in the mesentery of certain teleosti was reported by Brockmann (1846) and Stannius (1848), respectively. Thus the gland was named stannius corpuscle or Brockmann body. Later, as results of histological study, cells of stannius corpuscle tissues were constituted with Langerhans islet cells observed in mammalian pancreas by Diammare (1899) and Laguesse (1906). Thus, before the days of discovery of insulin by Banting and Best in 1921, stannius corpuscle has been interesting from the aspects of comparative anatomy and physiology. Rennie (1906) examined a large number of specimens in various species of teleosti and gave the term "principal islet" to easily recognizable stannius corpuscle. Osawa studied comparative anatomy in Freiburg and returned to Tokyo. He continued the study of comparative anatomy of Langerhans islet aand published a report on observation of "principal islet" of flatfish, limanda yokohamae Gth. in 1912 in Japanese. His report seemed to be a milestone of studies of fish insulin in Japan. Macleod attempted to demonstrate direct evidence on secretion of insulin from Langerhans islet cells. Experiments were made on extraction of "principal islet" of teleosti, angler Lophius) and sculpin (Myoxocephalus) to obtain insulin and demonstrated activity. No insulin activity was obtained from pancreatic tissues constituted with acinar cells of these fishes. In the case of elasmobranch, Langerhans islets are not separated, but potent insulin could be extracted from the pancreas. His report published in 1922 was the first report on fish insulin. Succeeding to Macleod's report, several reports on fish insulin were contnributed from Canada, England and U.S.A. until 1929. Dr. Kkumagai, Professor of Internal Medicine, Tohoku Imperial University (Sendai) also conducted the studies on extraction of active principle of pancreas since 1920, independently. But, a Toronto group reached the goal on discovery of insulin earlier than the Sendai group. The Sendai group also described extraction of active principle from the "principal islet" of teleosti. Especially, Ukai (1926) described morphological study on pancreas and stannius corpuscle for more than twenty species of fish. His report played an important role as the next milestone on the road of fish insulin development studies in Japan. In 1926, Dr. Sakaguchi who was a leading clinical diabetologist in Japan published a monograph entitled "Insulin" written in Japanese. He referred the report on fish insulins of McCormick and Noble and Dr. Kumagai's report, however, he commented that production of insulin from fish seemed to be less worthy due to requirements of laborious work to collect small stannius corpuscle from fish. Professor A. Ogata described a textbook entitled "Zoki-Yakuhin-Kagaku (chemistry of organotherapeutics): in 1931. In the first edition, papers of Macleod, McCormick, Dudley and Osawa were referred. In the revised fifth edition (1940) contained description of unpublished data of insulin content of various kinds of fish caught in Japan and supplied from his student Nagasawa. Under the circumstance of expanding tendency of the China Incident to World War II, shortage of importation and production of insulin preparations manufactured from domestic animals was anticipated. Development on manufacture of fish insulin became urgent. [Truncated]