Time-action profiles of the intermediate-acting insulin analogue des(64,65)-human proinsulin.
Des(64,65)-proinsulin (DPRO) is one of several endogenous intermediates arising during the conversion of proinsulin to insulin. In pharmaceutic preparations it is a clear solution containing no other proteins. Animal experiments and preliminary human studies indicated that DPRO should have a protracted time-action profile similar to that of NPH-insulin. Accordingly, we compared the time-action profiles of these two preparations, using the euglycaemic glucose clamp-technique in 9 healthy male volunteers. Different doses of DPRO (0.1, 0.15, 0.2 U/kg) or equipotent doses of NPH ( 0.2, 0.3, 0.4 U/kg) were injected subcutaneously into the abdominal wall. The maximal metabolic effect (GIRmax) of DPRO was greater than that of NPH-insulin (p < 0.05). With increasing doses, GIRmax differed significantly for DPRO but not for NPH-insulin. The time to maximal metabolic effect (tmax) was similar for the three doses of either preparation. However, tmax was reached 30 min earlier with DPRO than with NPH-insulin (p < 0.01). the decline to half-maximal after maximal activity was significantly faster with DPRO than with NPH-insulin (p < 0.0001). Subcutaneous injection of DPRO thus produced a time-action profile between that of regular insulin and NPH-insulin.
Heinemann
L
L
Dep of Nutrition and Metabolism, Heinrich-Heine-University Düsseldorf, Germany.
Heise
T
T
Klepper
A
A
Ampudia
J
J
Bender
R
R
Starke
A A
AA
D000328:Adult; D004305:Dose-Response Relationship, Drug; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007336:Insulin, Isophane / Q000493:pharmacokinetics*; D008297:Male; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D011384:Proinsulin / Q000493:pharmacokinetics*; D012016:Reference Values
D007004:Hypoglycemic Agents; D010446:Peptide Fragments; C088305:proinsulin, des(Lys(64),Arg(65)); D007336:Insulin, Isophane; D011384:Proinsulin