Effects of single and combined infusions of human biosynthetic proinsulin and insulin on glucose metabolism and on plasma hormone concentrations in euglycaemic clamp experiments.

Euglycaemic clamp experiments with single or combined infusions of human biosynthetic proinsulin and insulin were performed in 6 healthy, normal weight subjects in order to assess the possibility of antagonistic, additive, or synergistic effects on whole body glucose metabolism. Insulin (i: 2.02 pmol x kg-1 x min-1) or proinsulin (p: 9.26 pmol x kg-1 x min-1) were infused under euglycaemic clamp conditions over 240 min. After 120 min, the infusion rates were doubled (protocols ii and pp), or proinsulin (protocol ip) or insulin (protocol pi) infusions were added. After 240 min of infusing insulin or proinsulin alone, euglycaemia was maintained for an additional 60 min period without hormone infusions to measure the decay of hormone concentrations and of effects on glucose metabolism. Effects on glucose uptake were measured as the glucose infusion rate necessary to maintain euglycaemia. IR-insulin, IR-proinsulin, IR-C-peptide and IR-glucagon were determined by specific radioimmunoassays. After 240 min, similar steady state glucose infusion rates were reached for all protocols (mean +/- SEM, mg x kg-1 x min-1: ii: 10.6 +/- 1.0; ip: 9.1 +/- 0.4; pi: 10.0 +/- 0.9; pp: 8.4 +/- 0.7). The infusion rate with proinsulin alone (pp), however, was significantly smaller than with insulin alone (ii), indicating a somewhat lower effectiveness of the proinsulin dose employed. With all protocols, nonesterified fatty acid and IR-glucagon concentrations were decreased to a similar extent. Steady state hormone concentrations were reached within 30 min of each infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)