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 morphological background to putative nitric oxide and carbon monoxide pathways. Methods. Immunocytochemistry and confocal microscopy Results. After treatment with endotoxin, immunoreactivity for inducible nitric oxide synthase was expressed in a large number of islet cells, most of which were insulin-immunoreactive beta cells and in single glucagon-immunoreactive and pancreatic polypeptide-immunoreactive cells. Somatostatin-immunoreactive cells lacked immunoreactivity for inducible nitric oxide synthase. In untreated rats, immunoreactivity for constitutive nitric oxide synthase occurred in the majority of insulin-immunoreactive and glucagon-immunoreactive 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 constitutive and inducible haem oxygenase. Results. After treatment with alloxan, insulin-immunoreactivity was observed only in single islet cells, being almost devoid of immunoreactivity for constitutive nitric oxide synthase and haem oxygenase. Conclusion/interpretation. In vivo endotoxin-induced expression of inducible nitric oxide synthase in insulin-producing and in scattered glucagon-producing and pancreatic polypeptide-producing cells strengthens previous suggestions of a pathophysiological role for inducible nitric oxide synthase in the development of insulin-dependent diabetes mellitus. The presence of constitutive nitric oxide synthase and haem oxygenase in all four types of islet cells, together with recent functional data of ours support roles for nitric oxide and carbon monoxide as intracellular, paracrine or neurocrine modulators of islet hormone secretion.