Abstract. The occasional occurrence in sera of patients with Graves' disease of negative values in the assay for TSH receptor antibodies led to the discovery of endogenous antibodies to TSH. We examined the sera of approximately 2500 patients with Graves' disease. Eight positive sera were found. The IgG in all 8 sera showed higher binding with both bTSH and porcine TSH (pTSH) than with human TSH (hTSH). This means that autoantibodies to TSH in sera from patients with Graves' disease are rare and often directed towards heterologous bovine and porcine TSH. When hTSH levels were determined in sera of hyperthyroid patients with positive antibodies to hTSH, discrepancies in serum hTSH levels were observed when using different assay methods, i.e. hTSH levels were higher with the double-antibody technique, and lower with immunoradiometric assays. Antibodies in these sera showed higher binding to pTSH-α subunit than to -β subunit. The binding of the two pTSH subunits with antibodies could be displaced by intact bTSH. Neither stimulation in Graves' disease nor blocking in primary hypothyroidism of TSH receptor antibodies interfered with the binding of the anti-TSH antibodies to 125I-labelled pTSH, pTSH-α, and pTSH-β. Consequently, using this type of autoantibodies to TSH we were unable to obtain evidence that the TSH receptor antibodies of patients with Graves' disease was an anti-idiotype antibody against anti-TSH antibodies.
Y. Ochi, T. Nagamune, Y. Nakajima, M. Ishida, Y. Kajita, T. Hachiya and H. Ogura
T Miura, W Suzuki, E Ishihara, I Arai, H Ishida, Y Seino and K Tanigawa
BACKGROUND: In skeletal muscle and adipocytes, insulin-stimulated glucose transport has been known to occur through the translocation of glucose transporter (GLUT) 4 from the intracellular pool to the plasma membrane. The Tsumura Suzuki obese diabetic (TSOD) mouse, a new genetic animal model of type 2 diabetes, develops moderate degrees of obesity and diabetes that are especially apparent in animals more than 11 weeks old. A defect in insulin stimulation of GLUT4 translocation also contributes to the characteristics of type 2 diabetes. OBJECTIVE: To characterize this mouse further, we examined the alteration in insulin-stimulated GLUT4 translocation in the skeletal muscle and adipose tissue. METHODS: For glucose and insulin tolerance tests, the mice were given glucose or insulin and blood samples were collected. After isolation of low-density microsomal membrane and plasma membrane from skeletal muscle and adipose tissue, insulin-stimulated translocation of GLUT4 in these TSOD mice was examined by Western blot. RESULTS AND CONCLUSIONS: TSOD mice showed a significant increase in blood glucose after the glucose load, and exhibited a significantly attenuated decrease in blood glucose concentrations after administration of insulin, compared with that in control Tsumura Suzuki non-obese (TSNO) mice. The insulin-stimulated translocation of GLUT4 from low-density microsomal membranes to plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice. These results indicate that the reduced insulin sensitivity in diabetic TSOD mice is presumably due, at least in part, to the impaired GLUT4 translocation by insulin in both skeletal muscle and adipocytes.