Morphological evidence for the existence of nitric oxide and carbon monoxide pathways in the rat islets of Langerhans: An immunocytochemical and confocal microscopical study

Aims/hypothesis. To map the cellular location of inducible and constitutive nitric oxide synthase and haem oxygenase in rat islets to clarify the morp hological background to putative nitric oxide and carbon monoxide pathways. Methods. Immunocytochemistry and confocal microscopy Results. After treatment with endotoxin, immunoreactivity for inducible nit ric oxide synthase was expressed in a large number of islet cells, most of which were insulin-immunoreactive beta cells and in single glucagon-immunor eactive and pancreatic polypeptide-immunoreactive cells. Somatostatin-immun oreactive cells lacked immunoreactivity for inducible nitric oxide synthase . In untreated rats, immunoreactivity for constitutive nitric oxide synthas e occurred in the majority of insulin-immunoreactive and glucagon-immunorea ctive cells, in most pancreatic polypeptide-immunoreactive and somatostatin -immunoreactive cells and in islet nerves. Similarly, immunoreactivity for constitutive haem oxygenase was detected in all four types of islet cells. Endotoxin treatment did not change the pattern of immunoreactivity for cons titutive and inducible haem oxygenase. Results. After treatment with alloxa n, insulin-immunoreactivity was observed only in single islet cells, being almost devoid of immunoreactivity for constitutive nitric oxide synthase an d haem oxygenase. Conclusion/interpretation. In vivo endotoxin-induced expression of inducibl e nitric oxide synthase in insulin-producing and in scattered glucagon-prod ucing and pancreatic polypeptide-producing cells strengthens previous sugge stions of a pathophysiological role for inducible nitric oxide synthase in the development of insulin-dependent diabetes mellitus. The presence of con stitutive nitric oxide synthase and haem oxygenase in all four types of isl et cells, together with recent functional data of ours support roles for ni tric oxide and carbon monoxide as intracellular, paracrine or neurocrine mo dulators of islet hormone secretion.