STUDIES ON INSULIN RESISTANCE AND INSULIN RECEPTOR-BINDING IN MYOTONIA DYSTROPHICA

In an investigation of the mechanism of insulin resistance in myotonia dystrophica, insulin binding to circulating mononuclear cells was studied in 12 patients and compared to 12 matched controls. Mononuclear cells from fasting myotonia dystrophica and normal subjects were isolated in Ficoll-Hypaque mixture. The cells were incubated with [125I]insulin alone and in the presence of increasing amounts of unlabeled insulin. Monocytes were identified by esterase staining. The effect of normal and myotonia dystrophica sera on the binding of insulin to cultured human lymphocytes (IM-9) also was studied. Mean (±SEM) initial insulin-binding capacity in the myotonia dystrophica patients was 2.26 ± 0.36% of labeled insulin added per 50 X 106 mononuclear cells/ml. This capacity was significantly less than the 3.43 ± 0.43% (P < 0.001) obtained for the normal controls. In the 2 groups of 9 patients each in whom inhibition studies were done, the initial insulin-binding capacity normalized to 8 x 106 monocytes/ml was 1.65 ± 0.31% for the myotonia dystrophica group and 3.78 ± 0.13% (P < 0.001) for the control group. The addition of 12.5 ng/ml unlabeled insulin produced a significant decrease in the binding of labeled insulin in both groups, but the effect was significantly less (P < 0.01) in myotonia dystrophica compared with the normal group at 1.15 ± 0.13% (P < 0.05) and 1.97 ± 0.23% (P < 0.001), respectively. Examination of the data by Scatchard analysis and an average affinity profile indicated that the mean initial affinity of insulin receptors in myotonia dystrophica was significantly less (P < 0.01) at an affinity of 0.231 ± 0.064 nM‑1 compared to 0.496 ± 0.133 nM‑1 in the control group. No significant difference in receptor numbers was found. A positive correlation (r = 0.74; P < 0.01) was found between the reduced insulin-binding capacity to monocytes and the fall in plasma glucose in response to exogenous insulin (insulin resistance). There was no difference in the effect of the sera of myotonia dystrophica and normal subjects on insulin-binding capacity to cultured human lymphocytes. It is proposed that the reduction in insulin-binding capacity found in myotonia dystrophica is due to a decrease in affinity of insulin receptors, resulting in insulin resistance and a compensatory elevation of the plasma insulin levels. © 1979 by The Endocrine Society.