Endocrine pancreas: summary of observations generated by surgical fellows.

The present article summarizes scientific observations of the endocrine pancreas anatomy and physiology into a unifying hypothesis. The data were generated over the years by surgical fellows using human and rat isolated perfused pancreas models and in vivo islet microcirculation models. The endocrine pancreas secretes a hormonal milieu regulated by neural, hormonal, and nutritional stimuli and the microcirculation. Variation of the nutrient and hormone concentrations in the islet capillaries generates two levels of response. A first level of response is in the central nervous system (CNS). Cholinergic signals from the CNS regulate the islet microcirculation through internal and external gates. This regulation is mediated by nitric oxide (NO). The gates are endothelial cells found in feeding arterioles and capillaries of the islet capable of directing blood flow through changes in cellular shape. External gates shunt flow to the entire endocrine pancreas, and internal gates divert blood flow within the islet to expose selectively the appropriate cell type required for changes in hormonal milieu. The second level is within the islet. The islet cells respond directly to variations in hormonal and nutrient concentrations. There is extensive communication between the various types of islet cells regulated by NO and hormonal feedback loops. The two levels of response allow an appropriate hormonal milieu, which secreted into the bloodstream contributes to the maintenance of glucose homeostasis.