The relationship of red cell insulin binding to rate of weight gain during recovery from malnutrition - abstract

ABSTRACT

Chronic nutrient inadequacy, as exemplified by marasmus and kwashiorkor provides a model for insulin-binding studies. Red cell insulin receptors were studies in infants (age range 4 to 24 months) whilst malnourished and at 3 different stages of anthropometric recovery (60-84, 85-95, and 96-110 percent weight-for-height (EWH)). Four-hour fasting blood samples (3 ml) were used. Washed red cells (concentration 0.75 - 1.5x10 Esp 9/ml) were incubated at 15§C for 180 min in the presence of a constant amount of tracer (A[14] - I[125] - insulin, 16.6 - 1680 pM, 7 different concentrations). Non-specific binding was assessed by the radioactive insulin bound in 10,000 x the physiological range of insulin concentration. From the competitive binding curve, total binding, affinity and number of receptor sites were calculated by Scatchard analysis. Specific insulin-binding was expressed as the per cent of total A[14] -I[125]-insulin added at a cell concentration of 4x10Exp9/ml. Red cell specific insulin-binding (SB) in malnutrition (rate of weight change, (RWC) - 2.05ñ1.9 (10) g/kg/d) was 4.2ñ0.8 (12) percent. This was significantly less than at all three phases of recovery (p<0.01). At 60-84 percent EWH(RWC ñ 11.7ñ0.9 (20)), SB was 8.6ñ1.2 (20) percent at 96 -110 percent EWH (RWC ñ 0.95ñ1.1 (11)), SB was 8.8ñ1.4 (11) percent. A significantly (p<0.01) lower affinity of insulin for its receptor was shown in malnutrition, 0.9ñ0.2 (12) (Kx10Exp-8 M) than at other phases of recovery, 1.8ñ0.1 (24), 1.6ñ0.2 (20), and 1.4ñ0.4 (11) respectively. There were no significant changes in the number of receptor sites during malnutrition or during the catch-up growth phases. There was a highly significant positive correlation between rate of weight change and specific insulin-binding, (r= 0.45, p<0.0001 (67) as compared with plasma insulin concentration (r=0.33, p<0.01). Specific insulin-binding was also significantly correlated with the affinity of insulin for its receptor 9 r=0.28) p<0.05 (67)). Preliminary Results suggest that decreased protein, but not the carbohydrate or fat content of the diet, was associated with reduced insulin receptor affinity. Chronic nutritional inadequacy alters the affinity of the red cell receptor for insulin, leading to decreased binding, and this is quickly reversed early in rehabilitation. Decreased insulin-binding may be related to the carbohydrate intolerance of severe malnutrition (AU)