The effects of proinsulin pretreatment on the combined actions of insulin and proinsulin in normal man.
With the recent availability of biosynthetic human proinsulin there has been a renewed interest in evaluating its metabolic effects, either alone or in combination with insulin. It has been suggested that pretreatment with proinsulin enhances the hypoglycemic response to subsequently administered insulin. On the other hand, the simultaneous administration of proinsulin and insulin has additive, not synergistic, effects. To clarify this question we used the euglycemic glucose clamp technique in 10 normal subjects to compare the steady state effects on glucose disposal of combined infusions of insulin (0.54 microgram/M2 . min, equivalent to 15 mU/M2 . min) and proinsulin (2.75 micrograms/M2 . min) given both simultaneously and sequentially. The mean +/- SEM steady state glucose disposal rates were similar whether the two hormones were given simultaneously (7.2 +/- 0.7 mg/min . kg), after proinsulin pretreatment (7.7 +/- 0.7 mg/min . kg), or after insulin pretreatment (7.1 +/- 0.7 mg/min . kg). The serum proinsulin concentration of 5.39 +/- 0.3 pmol/ml during the infusion of proinsulin alone was unchanged by the simultaneous infusion of insulin, suggesting that in the doses used, insulin did not affect proinsulin clearance. We conclude that in normal subjects there is no enhancement of the combined action of insulin and proinsulin to stimulate glucose disposal by pretreatment with proinsulin or insulin.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D011384:Proinsulin / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin; D005947:Glucose