Biosynthetic human proinsulin, a new therapeutic compound for diabetics? A comparative study of biosynthetic human proinsulin with biosynthetic human insulin.
The biological activities of proinsulin, the endogenous precursor of insulin are different in comparison to insulin. Proinsulin has a longer biological half-life in serum and a much lower hypoglycemic potency. Biosynthetic human proinsulin has been suggested as an intermediate acting "insulin" in the treatment of diabetes mellitus, having the advantage of not including a retardation substance. For this reason it is important to establish a dose relationship in comparison to human insulin. Human proinsulin and human insulin were tested in 2 groups of healthy volunteers after i.v. application on a unit equivalent basis. 0.025, 0.05 and 0.1 units/kg of either compound were applied intravenously in a randomised order. Following human proinsulin application, the nadir of blood glucose showed a delay of 5-10 min. in comparison to insulin, however, the increase of blood glucose following the nadir was much more retarded after human proinsulin application. The antilipolytic effect of proinsulin was significantly stronger in comparison to insulin. No significant differences could be observed in the kinetics of beta-hydroxybutyrate levels and the counterregulatory response. Human proinsulin, based on a unit equivalent dosage, exerts a more pronounced hypoglycemic and antilipolytic effect, which is probably due to the longer biological half-life in comparison to insulin.
Rosak
C
C
Johann-Wolfgang-Goethe-Universität, Abteilung Endokrinologie, Frankfurt a.M., Germany.
Boehm
B O
BO
Althoff
P H
PH
Schöffling
K
K
D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006207:Half-Life; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D011384:Proinsulin / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D011388:Prolactin; D013006:Growth Hormone; D011384:Proinsulin; D020155:3-Hydroxybutyric Acid; D009638:Norepinephrine; D004837:Epinephrine