Summary
The hypoglycemic actions of human insulin (1 IU/kg b.w.) and biosynthetic human proinsulin
in about equimolar amounts were studied after intravenous and subcutaneous injection
in rabbits. Blood samples were taken up to four hours after injection for the determination
of blood glucose and immunoreactive levels of both insulin and human C-peptide. For
the determination of human C-peptide, serum taken after proinsulin injection was divided
into two fractions. One was examined directly by the human C-peptide radioimmunoassay
and the other after incubation with a protein-A-sepharose coupled insulin antibody
to find “free human C-peptide”.
Proinsulin in amounts equimolar to 1 IU insulin/kg b.w., exerted a 34% stronger hypoglycemic
action after subcutaneous injection than after intravenous administration (area under
curve estimation). Proinsulin-induced hypoglycemia did not last longer after intravenous
administration than that induced by intravenous insulin.
Although subcutaneous proinsulin did not show the same maximum decrease of blood glucose
compared to subcutaneous insulin, its action was significantly prolonged (up to 180
min).
Specific measurement of free human C-peptide showed no evidence of conversion of proinsulin
to insulin and C-peptide.
Key-Words
Human Proinsulin
-
Insulin
-
C-Peptide
-
Biological Activity
-
Pharmakokinetics
-
Rabbits
