Reduction in insulin receptors in amyotrophic lateral sclerosis correlates with reduced insulin sensitivity

Abnormal glucose and insulin metabolism have often been reported in patients with amyotrophic lateral sclerosis. Recently, we have demonstrated reduced insulin sensitivity in this disease and suggested that muscle wasting was not the principal determinant of this reduction. In the current studies, insulin binding to circulating mononuclear leukocytes from 10 amyotrophic lateral sclerosis patients and 16 controls were compared. The relative capacity and affinity of monocyte insulin binding sites were estimated, and simultaneous plasma insulin levels were also obtained. A 2 1/2-fold reduction in the number of binding sites (percent 125I-insulin bound to monocytes) was found in the patients compared with controls (p = 0.001). No differences were obtained when ED50 plots (relative affinity) were compared (p = 0.5). Ideal body weight was similar in both groups (approximately 100%) and plasma insulin levels were not elevated in the patients, suggesting that "down-regulation" from increased ambient hormone levels was not a factor in the lowered receptor numbers. A definite correlation was not found when numbers of insulin receptors were compared with disease progression, body weight, or plasma insulin levels. However, future studies with larger numbers of patients along with quantitation of disease progression may indicate such a trend.