Failure of Exogenous Insulin to Inhibit Insulin Secretion in Man

Abstract

In order to explore whether or not the negative feedback mechanism of insulin per se on insulin secretion exists in man, changes in plasma C-peptide immunoreactivity (CPR), as an index of pancreatic B cells secretory function, were studied in 6 nonobese healthy volunteers in the presence of high circulating levels of exogenous insulin. 10% glucose was infused concurrently so as to maintain blood sugar at the basal level. The insulin-glucose infusion was maintained for 120 minutes, achieving mean plasma levels of 140-180 mu1/ml. After this period, the insulin infusion was continued at the same rate for an additional 10 minutes while the glucose was omitted. Despite the elevated level of circulating insulin, no significant change in plasma CPR concentration was observed so long as the blood sugar was maintained at the basal levels. Following cessation of the glucose infusion, the plasma CPR levels declined with a decrease in blood sugar level. Under the conditions of the present study, no inhibitory effect of exogenous insulin on the secretory function of the B cells was noticed.

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

“…Apart from the question of positive feedback, there was no suppressive effect of exogenous insulin on CPR release in the perfused rat pancreas, to say the least. This is in essential agreement with the finding in our previous work on man (Shima et al, 1977) which demonstrated the inability of exogenous insulin to inhibit the secretory function of the B cell in the basal state. The conclusion we reached disagrees with that of Liljenquist et al (1978) who used a similar method.…”

“…The conclusion we reached disagrees with that of Liljenquist et al (1978) who used a similar method. In their study a much larger amount of insulin was administered for a longer period than in our previous in vivo study (Shima et al, 1977). In the present experiment we utilized the same amount as in the experiment of Loreti et al (1974) who used the largest amount of rat insulin ever employed in such experiments.…”

“…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) …”

The effect of glibenclamide on insulin secretion at normal glucose concentrations

“…Exogenous hyperinsulinaemia also presents the potential problem that insulin has been shown to have an inhibitory effect on its own secretion in vitro. Existing data as to whether this is significant in vivo is conflicting, with inhibition being found in some studies, but not in others [23][24][25][26]. While an inhibitory effect may lead to an underestimation of the secretory responses, the same insulin infusion rates were used in both the placebo and treatment arms in the current study and so would not be expected to affect the comparison between them.…”

Reduction of C-peptide secretion in noninsulin-dependent diabetic patients with long duration of insulin treatment.

“…Much work has been published supporting (Elahi et al, 1982;lijenquist et al, 1978;Beischer et al 1978;Greenfield et al, 1981;DeFronozo et al, 1981) and arguing against (Ohagawara et al, 1973;Shima et al, 1977;Sando et al, 1970) the possibility of feedback inhibition of endogenous insulin secretion by exogenous insulin.…”