Sequence of Cellular Events in Pancreatic Islets Leading to Impaired Insulin Secretion in Chronic Kidney Disease

The data obtained allow for the inference of the following formulation: as serum levels of PTH begin to rise, calcium entry into islets is augmented, which in turn will stimulate the activity of Ca2+ ATPase and the Na+-Ca2+ exchanger, and therefore, calcium extrusion out of the islets is increased. Thus, [Ca2+]i remains normal during the first 2 weeks of CRF. Activation of the Na+-Ca2+ exchanger may result in accumulation of sodium in the islets, an event that would activate the Na+-K+ ATPase. Because calcium entry is further augmented by the progressive rise in serum PTH levels, mitochondrial oxidation and ATP production would be reduced, resulting in lower ATP content. This fall in ATP causes a reduction in the Vmax of Ca2+ ATPase and Na+-K+ ATPase, and therefore calcium extrusion out of the islets is reduced; consequently, [Ca2+]i rises. With the decrease in ATP content and the rise in [Ca2+]i, glucose-induced insulin secretion is impaired because of alterations in the closure of ATP-dependent potassium channels and reduction in the glucose-induced calcium signal (Δ[Ca2+])i.