Erythrocyte Insulin Receptors in Non-Insulin-Dependent Diabetics before and after Treatment

On 40 non-insulin-dependent diabetes mellitus (NIDDM) patients who were hospitalized for the purpose of control and education of diabetes mellitus, erythrocyte insulin receptor assay was conducted with the used of 126l-insulin at the time of admission and the results obtained were compared with the results obtained from 98 normal subjects.
After an average of 20 days of treatment, erythrocytes insulin receptor assay was repeated and the effect of diabetes mellitus treatment on insulin receptor was examined. The mean specific 125l-insulin binding to erythrocytes in untreated NIDDM patients was significantly decreased (5.64 ± 0.30%, mean ± SEM) when compared with that of normal subjects (7.35 ± 0.20 %, p<0.001). The average native insulin concentration required for half maximum binding (HMB) of normal subjects and NIDDM patients before treatment were 3.1 and 5.4 ng/ml, respectively, and the mean affinity constants of the receptors of high affinity site (Ke) were 1.49 ± 0.05 and 0.75 ± 0.05 x 109M-1 (p<0.001), respectively. The insulin receptor number of high affinity site in untreated NIDDM patients was 33 ± 1.2 sites/cell, being significantly higher (p < 0.001) than that of normal subjects (22 ± 0.9 sites/cell).
After treatment of these patients, a marked decrease of blood glucose and a slight decrease of total cholesterol and triglycerides were observed with a concomitant significant increase of 126l-insulin binding to erythrocytes (from 5.64 ± 0.30% before to 6.68 ± 0.29% after treatment, p < 0.001). The average native insulin concentration required for HMB after treatment decreased to 4.2 ng/ml and Ke significantly increased to 1.12 ± 0.07 x 109M-1 (p<0.001). The mean concentration of receptors of high affinity site decreased to 28 ± 1.5 sites/cell after treatment.
The changes observed in erythrocytes insulin receptors by diabetes aimed at normalization of blood glucose level were similarly observed in the insulin (n = 13), sulfonylurea (n = 16), and diet treatment groups (n = 11).
No difference in the mean fasting plasma immunoreactive insulin (IRI) concentration was observed between normal subjects and untreated NIDDM patients and also no significant relationship could be demonstrated between fasting plasma IRI and specific 125l-insulin binding (%) to erythrocytes. A significant inverse correlation was observed between Ke and plasma lipids (total cholesterol r = -0.301, p < 0.02 and triglyceride r = -0.291, p<0.05), but no direct significant correlation could be demonstrated between Ke and fasting blood glucose (r = -0.220, p = NS).
These results indicate that: 1. Even in the absence of hyperinsulinemia in untreated NIDDM patients, there is a decrease in specific 125I-insulin binding to erythrocytes, which was found to be attributable to reduced affinity of the insulin receptors. 2. The number of erythrocyte insulin receptors of high affinity site was increased in untreated NIDDM patients, which was considered to be a phenomenon to compensate for decrease in affinity. 3. The affinity of the insulin receptors of NIDDM patients improved following treatment and the receptor number of high affinity site also approached that of normal level, suggesting reversibility. 4. The effect of treatment on erythrocytes insulin receptors of NIDDM patients was similarly observed in the insulin, sulfonylurea and diet treatment groups, indicating that it could not be a direct effect of the drugs. 5. Normalization of intracellular metabolism of the post receptor level after treatment may have served as an important factor in the improvement of erythrocyte insulin receptors of NIDDM patients.