Abstract
We analyzed type II pneumocytes, isolated to purity from adult rabbits, for the presence of insulin receptors. Assays were performed on cells cultured for 24 hours in Eagles minimal essential medium. Insulin binding to cells in culture approached a steady-state level by 180 minutes and remained constant for at least one hour. Competition experiments using native insulin, proinsulin, and desoctateptide established specificity of binding. Scatchard analysis of binding revealed a class of high affinity receptors (Kd = 1.5 × 10−10 M) and a low affinity component (Kd - 4 × 10−9M). The number of receptors was estimated at 2,000 - 4,000/cell. Insulin added to cultures at physiologic concentrations produced a 60% increase in incorporation of labelled glucose into cellular fatty acid and in incorporation of choline into phosphatidylcholine. A dose response relationship was demonstrated. The presence of insulin receptors on type II pneumocytes and the effect of insulin on phospholipid synthesis suggest a mechanism for the disorder of surfactant synthesis in infants of diabetic mothers: chronic hyperglycemia & hyperinsulinemia leads to diminished reactivity ("down-regulation") of insulin receptors during fetal life; in late gestation and after birth the hyporeactive insulin receptors do not allow sufficient substrate into cells for surfactant synthesis.
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Shapiro, D., Livingston, J., Maniscalco, W. et al. INSULIN RECEPTORS AND EFFECTS ON TYPE II PNEUMOCYTESAN HYPOTHESIS FOR THE ETIOLOGY OF DECREASED SURFACANT SYNTHESIS IN INFANTS OF DIABETIC MOTHERS. Pediatr Res 18 (Suppl 4), 346 (1984). https://doi.org/10.1203/00006450-198404001-01519
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DOI: https://doi.org/10.1203/00006450-198404001-01519