Neurohormonal regulation of pancreatic secretion

Abstract

Recent advances in the regulation of pancreatic secretion by neural and hormonal mechanisms are discussed in this review. It has been shown that the multidrug-resistance protein MRP4 may play a role in the efflux of cAMP from exocrine cells and neurokinin receptors are important in substance P-mediated inhibition of ductal bicarbonate secretion. Leptin attenuates glucagon secretion by downregulating glucagon gene expression, whereas ghrelin upregulates glucagon release by elevating intracellular calcium and phosphorylation of extracellular signal-regulated kinase (ERK). Cytokine interleukin 6 is secreted from muscles during exercise and induces the release of GLP-1 that stimulates insulin secretion. Osteocalcin and 17β-estradiol mediate their effects through G protein-coupled receptors, resulting in ERK phosphorylation and activation of protein kinase-dependent signaling pathways. Melatonin and ghrelin inhibit insulin secretion through inhibitory G proteins, whereas aldosterone may attenuate insulin secretion by increasing oxidative stress in islets cells. Finally, the pattern of innervation of human pancreatic islets has been examined and demonstrated to be very different from that in the mouse. Many different receptors and signaling pathways govern the complex biology of pancreatic secretion. Elucidation of these cellular mechanisms will aid in drug discovery and treatment as well as prevention of pancreatic diseases.