Studies on Insulin Resistance and Insulin Receptor Binding in Myotonia Dystrophica*

Abstract

In an investigation of the mechanism of insulinresistance in myotonia dystrophica, insulin binding to circulatingmononuclear cells was studied in 12 patients and compared to12 matched controls. Mononuclear cells from fasting myotoniadystrophica and normal subjects were isolated in Ficoll-Hypaquemixture. The cells were incubated with [125I]insulin alone and inthe presence of increasing amounts of unlabeled insulin. Monocyteswere identified by esterase staining. The effect of normaland myotonia dystrophica sera on the binding of insulin tocultured human lymphocytes (IM-9) also was studied. Mean(±SEM) initial insulin-binding capacity in the myotonia dystrophicapatients was 2.26 ± 0.36% of labeled insulin added per 50×106 mononuclear cells%ml. This capacity was significantly lessthan the 3.43 ± 0.43<; (P < 0.001) obtained for the normalcontrols. In the 2 groups of 9 patients each in whom inhibitionstudies were done, the initial insulin-binding capacity normalizedto 8 × 106 monocytes/ml was 1.65 ± 0.31% for the myotoniadystrophica group and 3.78 % 0.13% (P < 0.001) for the controlgroup. The addition of 12.5 ng/ml unlabeled insulin produced asignificant decrease in the binding of labeled insulin in bothgroups, but the effect was significantly less (P < 0.01) in myotoniadystrophica 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 averageaffinity profile indicated that the mean initial affinity of insulinreceptors 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 inreceptor numbers was found. A positive correlation (r = 0.74; P< 0.01) was found between the reduced insulin-binding capacityto monocytes and the fall in plasma glucose in response toexogenous insulin (insulin resistance). There was no differencein the effect of the sera of myotonia dystrophica and normalsubjects on insulin-binding capacity to cultured human lymphocytes.It is proposed that the reduction in insulin-binding capacityfound in myotonia dystrophica is due to a decrease in affinityof insulin receptors, resulting in insulin resistance and a compensatoryelevation of the plasma insulin levels. (J Clin Endocrinology Metab49: 216, 1979)