A TRYPSIN INHIBITOR IN THE VISCERA OF JAPANESE COMMON SQUID (TODARODES PACIFICUS) ELICITS INSULINOTROPIC EFFECTS IN DIABETIC GK RATS

The potential use of trypsin inhibitors (TI) present in the viscera of Japanese common squid (Todarodes pacificus) was examined for diabetes treatment. In a single-glucose tolerance test, the crude TI (C-TI) fraction significantly stimulated insulin secretion by normal Wistar rats and by diabetic GK rats. The highly purified TI (H-TI) fraction displayed the same effect on the glucose tolerance test with the GK rats. The TI activity of C-TI was not decreased by pepsin or chymotrypsin digestion in vitro, and the C-TI fraction did not have α-glucosidase inhibitory activity. These results indicate that the substance with the stimulating effect on insulin secretion in rats is the squid TI and that the hypoglycemic effect on glucose tolerance in GK rats is related to an improvement of insulin secretion due to the squid TI. PRACTICAL APPLICATIONS In previous study, the biochemical properties and hypoglycemic effects of squid trypsin inhibitor on diabetic GK rats were analyzed. Here, we showed its resistance to digestive enzyme such as chymotrypsin and pepsin. Further squid trypsin inhibitor stimulates the insulin secretion in GK rats. These results clearly suggests that squid TI retains its activity in duodenum and stimulates the secretion of cholecystokinin which induce the insulin secretion in pancreas. Therefore, squid visera trypsin inhibitor is a potent reagent for lowering blood glucose level.