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Intermediate and long-acting insulin preparations without protamine sulphate are complement activators in vitro
J Duchateau1, H Schreyen, H Dorchy
1Department of Immunology, Saint-Pierre University Hospital, Brussels, Belgium.
Diabete & Metabolisme
|July 1, 1992
Summary
Certain long-acting insulins without protamine sulfate activate complement in vitro. Protamine sulfate inhibits this activation, suggesting it stabilizes insulin crystals and prevents complement consumption. Short-acting and NPH insulins do not activate complement.
Area of Science:
- Immunology
- Endocrinology
- Biochemistry
Background:
- Abnormal complement metabolism observed in Type 1 diabetic children on specific insulin therapies.
- Previous findings suggest a link between insulin preparations and complement system activity.
Purpose of the Study:
- To investigate the in vitro complement-activating potential of various insulin preparations.
- To determine the role of protamine sulfate in modulating insulin-induced complement activation.
Main Methods:
- Incubation of healthy donor serum with commercial insulin preparations (rapid, intermediate, long-acting).
- Measurement of C3d levels as a marker of C3 complement fraction consumption using turbidimetry.
- Assessment of protamine sulfate's inhibitory effect on complement activation and its dose-dependency.
Main Results:
- Long-acting insulins lacking protamine sulfate significantly increased C3d levels, indicating complement activation.
- Protamine sulfate addition dose-dependently inhibited complement activation, with maximal effect at NPH insulin concentrations.
- Insulin crystals were rapidly cleared in serum with protamine sulfate, suggesting interference with surface properties.
Conclusions:
- Specific protracted insulin preparations, devoid of protamine sulfate, can activate the complement system in vitro.
- Protamine sulfate appears to inhibit complement activation by altering the physical nature of insulin crystals.
- Short-acting and NPH (neutral protamine Hagedorn) insulins were found not to be complement activators.