Transient glucose intolerance in rats after a single injection of serum from a diabetic patient with an unusual insulin resistance.
The single intravenous injection to rats of 1 ml of serum from an insulin resistant patient without an excessive titre of insulin antibodies (total extractable insulin levels: 0.8 U/l, serum insulin binding capacity: 1.58 U/l) and no demonstrable insulin receptor antibodies, produced fasting hyperglycemia in the animals on the fourth day following the injection (FPG: 212 +/- 35 mg %). On the 7th day the FPG returned to normal but the IVGTT was still pathological. After 14 days there was complete normalisation of the IVGTT. Glucose intolerance did not occur when rats were injected with 1 ml of the following control sera: the patient's serum following 6 months of treatment with cyclophosphamide when her insulin resistance was in remission, pooled sera from IDD's without insulin resistance, serum from an insulin resistant IDD with a high titre of insulin binding capacity (greater than 40 U/l) or with serum from a normal human subject. There were no alterations on light microscopy of the pancreatic islets of rats sacrificed on the 4th or 21st days. The above data suggest that our patient carried an uncharacterised substance which was capable of inducing glucose intolerance in rats. Hypothetically, it may be postulated that it was an immunoglobulin or some other protein acting via downregulation of insulin receptors or interfering with a post-receptor event mediating insulin action.
D000818:Animals; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors