Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.
OBJECTIVE
To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology.


METHODS
Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue.


METHODS
Study in normal people at a diabetes research unit and a university department of medical physics.


METHODS
Seven healthy male volunteers aged 20-39 not receiving any other drugs.


METHODS
After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days.


METHODS
To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue.


CONCLUSIONS
The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.
Vora
J P
JP
Department of Medicine, University of Wales College of Medicine, Health Park, Cardiff.
Owens
D R
DR
Dolben
J
J
Atiea
J A
JA
Dean
J D
JD
Kang
S
S
Burch
A
A
Brange
J
J
D000042:Absorption; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D011897:Random Allocation; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; C058172:insulin, Asp(B9)-Glu(B27)-