Diabetes, Vol 44, Issue 12 1381-1385, Copyright © 1995 by American Diabetes Association

ARTICLES

Action profile of cobalt(III)-insulin. A novel principle of protraction of potential use for basal insulin delivery

P Kurtzhals and U Ribel
Novo Research Institute, Novo Nordisk A/S, Bagsvaerd, Denmark.

The Co(3+)-insulin hexamer is an extraordinary stable insulin hexamer that has no affinity for the insulin receptor per se but is converted into active insulin in vivo. In the present study, we evaluated the action profile of Co(3+)-insulin after subcutaneous injection into nondiabetic pigs and showed that the Co(3+)-hexamer does not dissociate before absorption. After absorption, Co(3+)-insulin is accumulated in the bloodstream because the complex is distributed and eliminated more slowly than human insulin. The degree of protraction of Co(3+)-insulin is similar to that of NPH insulin when evaluated in an euglycemic glucose clamp. We suggest that the long plasma half-life and a gradual in vivo activation contribute to prolong the effect of Co(3+)-insulin. The Co(3+)-insulin hexamer provides a novel principle of protraction of potential use for basal insulin delivery to the diabetic patient.
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