We studied a patient with Acanthosis nigricans and the type B syndrome of severe insulin resistance. The patient's rates of basal glucose disappearance and appearance were both normal (2.2 and 1.7 mg/kg . min, respectively). FFA, betahydroxybutyrate, and acetoacetate concentrations were stable at 0.8, 1.0, and 0.3 mM, respectively, during a 2-h saline infusion after an overnight fast, indicating continued presence of insulin-like activity (ILA) in her serum. Infusion of insulin at rates of 2.7 and 27 U/h, raising peripheral insulin concentrations from 1400 to 4000 and 6000 microU/ml, respectively, had no effect on glucose disappearance and appearance or plasma concentrations of beta-hydroxybutyrate, acetoacetate, and FFA, suggesting that the observed ILA was not caused by the patient's plasma insulin. To determine the source of the ILA we used the patient's serum containing antiinsulin receptor antibodies (AIRA) to study its acute (2 h) and chronic (24 h) effects on insulin binding and glycogen synthesis in rat hepatocytes in primary culture. Preincubation of hepatocytes with AIRA serum (diluted 1:100) inhibited insulin binding by 84% and 88% after 2 and 24 h, respectively. It increased U-[14C]glucose incorporation into glycogen by 40% and 52% after 2 and 24 h, respectively. These effects were not caused by insulin present in the patient's serum. We conclude that AIRA serum, in addition to causing severe insulin resistance through inhibition of insulin binding, also exerted strong and long lasting insulin-like effects. These findings are compatible with the patient's clinical features of absence of ketoacidosis despite severe insulin resistance, decrease in glucose concentrations during fasting, and postprandial hyperglycemia.

The Japan Red Cross started screening donated blood for anti-HCV in Nov. 1989. Approximately 0.9% of donors were found to be positive by the 1st generation antibody test. The authors started a carrier clinic for the medical care of apparently healthy HCV carriers. Donors whose antibodies were strongly positive both by 1st EIA and 2nd PHA were informed, and were confirmed by RIBA 2 and RT-PCR. A total of 262 carriers (150 males and 112 females) with mean age of 46.8 +/- 11.2 yrs have visited the clinic. Of these carriers 149 were diagnosed to be asymptomatic clinically, biochemically and echographically. Eighty-seven carriers had received blood transfusions 22.7 +/- 10.9 yrs previously, while 106 had had acupuncture. Sixty had a family history of liver disease. Fifty-four had a history of heavy alcohol intake. Tattoos and/or iv drug abuse were found in 11, and nosocomial needle accidents in 4. HBV antibodies were found in 145 cases (55%). In conclusion, approximately 60% of HCV carriers found at the time of blood donation were apparently asymptomatic, suggesting the need of longer follow-up. Main routes of infection were estimated to be blood transfusion (33%), other parenteral exposure routes (6%), household (10% or less), and acupuncture (20% or less), considering duplication and priority.

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The interactions of fluorescein-isothiocyanated porcine insulin (FITC-insulin) with human platelets were examined by a fluorescence polarization technique. The degree of polarization of the incubation mixture of FITC-insulin and platelets was changed by the ratio of bound to free insulin. This method enabled us to follow the time course of the reaction in the homogeneous assay system without separating the insulin-receptor complex, and it was shown to be useful in the study of insulin binding and dissociation. Insulin binding to trypsinized platelets was considered to be nonspecific, since this fraction remained relatively constant during the incubation period at 25 C. Specific binding was evaluated by subtracting the nonspecific binding from the binding to untreated platelets; specific binding reached a plateau at 60 min. Scatchard analysis was conducted by adding increasing amounts of FITC-insulin to a platelet suspension. Furthermore, some of the prerequisites in analyzing insulin-receptor interaction were examined by this method.

Sera and their IgG from 10/104 diabetic patients (five with insulin-dependent and five with noninsulin-dependent diabetes, NIDDM), contained antibodies that bound 125I-labeled purified human insulin receptors. 9 of these 10 sera failed to inhibit insulin binding (to rat hepatocytes and human placental membranes), did not stimulate glucose oxidation (by isolated rat adipocytes), and did not bind human placental IGF-1 receptors. Only one serum (and its IgG) modestly inhibited insulin binding and stimulated glucose oxidation. We conclude (a) that sera from 9/104 diabetics (five insulin-dependent and four noninsulin-dependent) contained a newly identified species of IgG antiinsulin receptor autoantibodies (AIRA), which bound to the insulin receptor at a locus different from the insulin binding site and did not inhibit insulin binding; and (b) that only 1/104 diabetic sera contained low-titer "conventional" antiinsulin receptor autoantibodies that bound to the insulin receptor at or near the insulin binding site, inhibited insulin binding and caused a clinical condition, which was difficult to distinguish from typical NIDDM.