Effect of Prior Infusion of Exogenous Bonito Insulin on Glucose-Induced Insulin Release in Man

Abstract

SynopsisIn order to investigate a possible short feedback mechanism of insulin secretion, the effect of prior infusion of bonito insulin upon glucose-induced insulin secretion in man was studied. The increase in plasma insulin after intravenous injection of a glucose solution was analysed under prior sustaining infusion of bonito insulin at the concentration of 12mU/0.5ml/min and 6mU/0.5ml/min.These concentrations of bonito insulin were shown to have had no effect on the blood sugar levels, nor on the basal insulin levels. After the prior eight hour infusion of exogenous insulin, the increase in glucoseinduced insulin secretion was significantly smaller than that produced after infusion of saline as a control. The magnitude of the inhibition in plasma insulin elevation was more remarkable at the higher dose of insulin. The level of blood sugar after glucose injection shown no significant change.The half-life of immunoreactive insulin in plasma was determined after prior infusion of bonito insulin or saline for three hours. There was not tendency to any difference in T 1/2 between saline treated subjects and subjects who had received the rapid injection of porcine insulin prior to the infusion of bonito insulin.

Effect of Exogenous Bonito Insulin on Endogenous Insulin Secretion in Dogs

“…We found that the systemic infusion of small doses of exogenous bonito insulin which proved inert on the blood sugar levels, resulted in an inhibition of endogenous insulin secretion in man, and there was a lag in the feedback mechanism (Ohgawara et al, 1973). Further, in this study, the prolonged infusion of exogenous bonito insulin appeared to inhibit both the basic insulin secretion and the biphasic pattern in glucose-induced insulin release.…”

“…We found previously that the systemic infusion of a small dose of bonito insulin which proved inert on the blood sugar levels resulted in an inhibition of glucose-induced insulin secretion in man (Ohgawara et al, 1973), and that the infusion of exogenous insulin for a long period is necessary to inhibit the glucose-induced insulin response. It is very important and interesting that there is a lag in this feedback mechanism.…”

Effect of the bonito insulin on the insulin release from monolayer culture of rat pancreas.

“…Previously, we found that the infusion of a small dose of bonito insulin, which was ineffective on the blood sugar levels, resulted in an inhibition of glucose-induced insulin secretion in man and dogs (Ohgawara et al, 1973 and1974), but more than 20 hr of insulin infusion was necessary to inhibit the glucose induced insulin secretion. It still remains to be established whether a direct or indirect feedback mechanism is responsible for this inhibition.…”

“…The cross-reactivity of bonito insulin with rat insulin in our assay system is less than 5%, therefore that is almost negligible. (Ohgawara et al, 1973 and1974). (Hahn, 1971 ;Iversen, 1971;Ammon et al, 1973 ;Sodoyez et al, 1969 …”

Failure of exogenous insulin to inhibit C-peptide release from the perfused rat pancreas.

“…Grodsky (1968), Malaisse et al (1968) and Sando et al (1970) denied the possibility of a feedback mechanism by which insulin secretion is inhibited by insulin itself. On the other hand there were an equivalent or greater number of contrasting data which pointed to the possible existence of the mechanism (Morgan et al, 1965;Logothetopoulos et al, 1965;Iversen and Miles, 1971;Ziegler et al, 1972;Ohgawara et al, 1973). A couple of studies (Shima et al, 1977;Liljenquist et al, 1978) …”