Effects of intestinal adaptation on insulin binding to villus cell membranes

Insulin affects the expression of brush border enzymes by villus cells in vitro and in vivo. Physiological (lactation) and surgical (jejunoileal bypass) models of hyper- and hypoplasia were established so that insulin receptor characteristics could be related to villus histology, expression of sucrase and alkaline phosphatase, and plasma insulin concentrations. In lactating rats, villus height increased up to 55% (p less than 0.005), and fasting plasma insulin increased 71% (p = 0.005), compared with controls. Insulin binding to villus cell membranes, and sucrase and alkaline phosphatase activities were, however, unchanged. In ileum of bypass operated rats, villus height increased 134% (p less than 0.005) while insulin binding fell 68% (p = 0.025). Scatchard analysis revealed that this was largely because of reduction in binding by high affinity receptors. Sucrase and alkaline phosphatase specific activities fell 57% (p = 0.03) and 49% (p = 0.02) respectively, suggesting that ileal villus cells were hypomature. The slightly hypoplastic tissue of selfemptying loops showed normal insulin binding compared to jejunum of sham operated controls. Bypass and sham operated rats had similar fasting plasma insulin concentrations. Reduced insulin binding in markedly hyperplastic gut of bypass operated rats might reflect hypomaturity of villus cells. The reduction in insulin binding, however, might significantly modulate the effect of insulin on small intestinal mucosa and account for the fall in enzyme activity which occurs despite villus hyperplasia.