"Insulin Receptor Antibody" Found in a Case of SjÖgren Syndrome Associated with Extreme Insulin Resistence Diabetes

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Recently, Flier, Kahn, Roth andBar 1) reported circulating antibody that impair insulin receptor binding in patients with an unusual diabetic syndrome and extreme insulin resistance. The same one was found in a 44 yrs. female who had been suffered from extreme insulin resistance diabetes associated with well documented SjÖgren syndrome 2 ). Biopsy of sublingual salivary glands, sialography of subauricular glands proved the chronic inflammation. Dry skin, xerostomia, keratoconjunctivitis, disturbance of lacrimation, positive urine protein were disclosed together with a high amount of gamma-globulin, 3.5g/dl. Other laboratoryfindings showed in the TABLE I. After several months of steroid therapy to the original disease, loss of weight, glycosuria and hyperglycemia were happenly noticed. No good control was succeeded in management of blood glucose, in spite of daily maximum 6, 600 unit of rapid insulin given. Predonisolone and/or endoxan failed to reduce the blood glucose level. Due to vascular hardenenig, insulin therapy could not help discontinuing. 450mg of buformin could maintain the level at around 300mg/dl (Fig. 1).<BR>Basal and glucose stimulated IRI were always demonstrated more than 10 to 100 times of normal control (Fig. 2). No significant insulin binding antibody was found with Sephadex column gel filtration (Fig. 3). Ketosis or metabolic acidosis have never been observed through the entire course. Glucose uptake by her own whole blood and by the fat cell of mouse (FILA) were absolutely abolished compared to control, so that some factor in her blood might interfere the glucose uptake into blood cells or mouse fat cell.<BR>The circulating insulin receptor antibody found by Flier etal. was revealed in her serum too, demonstrating the high titer, that is, less than 10% of normal insulin bindig to the cultured lymphocyte (IM-9 line) with one hour preincubation in 1 to 12 dilution of her serum, 37% in 1 to 120 dilution and 90% in 1 to 1,200 dilution (Fig. 4). Kahn et al. 3) reported six patients who were suffered from extreme insulin resistence diabetes. Their clinical features were described as such, 1) female, 2) ages 12-50, 3) sporadic occurence, 4)hyperglycemia, hypoglycemia, hirsutism, accelerated growth, 5) neither obese nor lipoatrophic, 6) variable degree of acanthosis nigricans, 7) extraordinary insulin resistance in the absence of the usual known causes, 8) marked decrease in insulin binding to its receptors, 9) spontaneous improvement or remission in some patients and 10) sign and symptomes suggestive of an autoimmune-diseases in some patients. Three of them exhibited "insulin receptor antibody" in their own blood serum which may interfere insulin binding at the site of insulin receptor, resulting in uneffectiveness of large amount of serum insulin, endogenous or exogenous. This is the fourth case which found antibody though no established acanthosis nigricans revealed. Furthermore, it is very interesting that this case was combined with SjÖgren syndrome which is thought to be one of the autoimmune diseases and had been proved a big amount of gamma-globulin in the serum. Flier et al. clarified that the inhibitory activity was precipitated by 33% ammonium sulphate and recovered almost quantitatively in the redisolved precipitate. And rabbit antisera to human immunoglobulins could precipitate the inhibitory activity in parallel with the immunoglobulins.<BR>Alternatively, the recent study on insulin receptor has developed strikingly. Number of insulin receptor on the cell surface decreased in obesity which is known as high level of IRI and in some cases of diabetes so that insulin activity diminished in these occaisions 4). Eventually, above mentioned antibody might play a role to reduce number of insulin receptor on the cell surface, acutely or chronically in many cases of obesity and diabetes, which are not able to be identified as having the antibody by this method. Thus,
Japan Society of Clinical Chemistryの論文

"Insulin Receptor Antibody" Found in a Case of SjÖgren Syndrome Associated with Extreme Insulin Resistence Diabetes

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