874 INSULIN RECEPTORS IN CYSTIC FIBROSIS (CF): INCREASE IN RECEPTOR NUMBER MAY EXPLAIN INSULIN SENSITIVITY

Abstract

Specific 125I insulin binding to circulating monocytes was studied in a group of 13 patients with CF, 4 of whom were insulin dependent. Nine untreated patients had mild carbohydrate intolerance in response to oral glucose as compared to controls (201±26mg/dl vs.103±6 M±SEm at 2h; 144±26 vs.92±5 at 3h). The peak insulin response was delayed to 2 hours in CF and lower than the one hour peak of normals (44mIU/ml vs.66mIU/ml). Calculated insulinogenic index, II (∑Δinsulin/∑Δglucose) was lower for CF than controls (0.21±0.05 vs.0.37±0.04 p<0.01), indicating enhanced insulin sensitivity. Scatchard analysis of insulin binding revealed a marked increase in receptor sites in untreated CF patients as compared to controls; 44,000 sites/cell vs. 25,000 sites/cell. Specific insulin binding at tracer concentrations (0.3ng/ml) was lower in CF 3.14% vs.5.14%, and the calculated affinity constant for binding (Ke) was reduced, 0.8x108 M−1 vs. 2.5x108 M−1. Insulin treated patients did not have lower receptor numbers or altered affinity as compared to the untreated. Thus 1) in CF diminished insulin secretion is associated with an increased number of receptor sites 2) increased binding sites would explain sensitivity to endogenous insulin, as demonstrated by the decreased II as well as to exogenous insulin (reported by others) 3) the consequences of the substantial increase in receptor number may be offset somewhat by reduced receptor affinity.