Failure of human insulin to influence endogenous basal insulin secretion in mild diabetics

Abstract

In evaluating the possibility of self-regulation of insulin secretion in man, human insulin may be more appropriate as an inhibitor to be considered than insulins from other species because the differences in the structure of the hormones might play some part in this conflicting proposal. The present study was carried out to examine whether human insulin per se can exert a feedback effect on the insulin secretion of B-cell in mild diabetics under physiologic condition. Fifteen mild diabetics were given a two-hour infusion of human insulin at a constant rate of 40 mU/m/min after a priming dose of 160 mU/m/min for the first two minutes. The plasma glucose in nine of these patients were maintained at their basal level of 92.8 ± 3.7 mg/dL (Group A) with a glucose clamp technique (the coefficient of variation = 5.0 ± 0.8% during the clamp), while that in the remaining six patients were intentionally altered, within physiologic range, from 114.5 ± 8.4 mg/dL to 83.8 ± 4.9 mg/dL (Group B). During insulin infusion the plasma immunoreactive insulin (IRI) level were well-maintained at about 50 μU/mL level in both groups, whereas the C-peptide reactivity (CPR) in group B decreased from 1.28 ± 0.15 ng/mL to 0.59 ± 0.14 ng/mL in parallel to the change of plasma glucose, in contrast to the relatively stable CPR level of 0.92 ± 0.08 ng/mL in group A. When the correlation of these parameters in all cases, in order to avoid the influence of grouping, as expressed by the total change of plasma glucose (ΣΔPG), C-peptide (ΣΔCPR), insulin (ΣΔIRI), and glucagon (ΣΔGI) were examined, ΣΔCPR was significantly correlated to ΣΔPG ( r = .82, P < .001) and less to GI ( r = .76, P < .001), but not to ΣΔIRI at all. Moreover, when a multiple regression analysis was performed using ΣΔCPR as the function of ΣΔPG, ΣΔIRI, and ΣΔGI, IRI also is shown to exert the least influence on CPR. These data suggest that under physiologic conditions the plasma glucose-B-cell interaction and/or to a lesser extend the glucagon-B-cell interaction rather than the negative feedback mechanism of insulin is of prime importance in controlling the B-cell function in mild diabetics.