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  • 1
    ISSN: 1432-1440
    Keywords: Insulin-autoimmune syndrome ; Insulin autoantibodies ; Autoimmune disease ; Hypoglycemia ; HPLC ; Insulin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 µU/ml (normal range 〈20 µU/ml) were detected which rose to peak levels of 2,460 µU/ml (normal range 〈300 µU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation).125I-insulin added to the patient's serum was not bound to dextrancoated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 µU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-8580
    Keywords: Camostate (FOY 305) ; Degradation ; Rat liver ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The elimination of the low molecular weight proteinase inhibitor camostate (FOY 305) was studied in rats after oral administration and in the the situ perfused rat liver. After feeding of camostate (400 mg/kg b. w.) only the metabolites (FOY 251, GBA) were detected in blood samples withdrawn from the portal and hepatic vein. This indicated a rapid degradation of FOY 305 after absorption from the gut lumen. The hepatic extraction of the anti-proteolytic active metabolite FOY 251 during a single liver passage was 23%. It remained almost constant over the period of 120 min. In the perfused rat liver, FOY 305 was given in concentrations comparable to the in vivo studies. It was eliminated by 20%. In these experiments, the compound was metabolized to FOY 251 and in minor amounts to guanidino-benzoate (GBA), the latter being an anti-proteolytic ineffective degradation product. In conclusion, a low hepatic extraction of FOY 305 led to pharmacologically effective concentrations of the active metabolite FOY 251 in the circulation after oral ingestion of the proteinase inhibitor.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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