Insulin resistance caused by massive degradation of subcutaneous insulin.
Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not inhibited by N-ethylmaleimide. The soluble fraction also degraded glucagon and B chain but not growth hormone or myoglobin. It was inhibited by incubation with the patient's nonketotic sera, normal sera, or Trasylol. Glutathione-insulin-transhydrogenase (GIT) activity was 66% of normal. The biopsy of adipose tissue at remission showed a normal level of insulin- and glucagon-degrading activity. The activity was eluted from Sephadex G200 as a single peak and had properties consistent with those of the insulin-specific protease (ISP). The increased degrading activity present during insulin resistance had properties not shared with ISP, suggesting the presence of an uncharacterized protease.
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D016883:Diabetic Ketoacidosis / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D007333:Insulin Resistance
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005033:Ethylmaleimide