Emerging Role of Nitric Oxide in Pancreas and Pancreatic Islet Transplantation

Transplantation of whole pancreas or pancreatic islets represents β-cell replacement therapy that is now clinically viable after several years of experimental investigations and failed clinical attempts. This form of therapy is a definitive alternative to intensive insulin-based regimen for a subset of T1DM patients who have long-term diabetic complications or experience severe hypoglycemic unawareness or are likely to develop these, as well as those with intractable pain associated with chronic pancreatitis. While whole-pancreas or islet transplantation provides a long-term normoglycemic status without exogenous insulin administration, there are major downsides such as graft pancreatitis arising from ischemia-reperfusion injury (IRI) after whole-pancreas transplantation, and apoptosis of islets after isolation, hence requiring high number of islets from more than one donor in islet transplantation. Nitric oxide, a ubiquitous molecule and the first identified member of a family of gaseous signaling molecules, is emerging as a suitable candidate to combat IRI and protect against islet apoptosis, and prevent complications after whole-pancreas or islet transplantation. In this chapter, the author discusses the therapeutic benefits of nitric oxide in experimental models of whole-pancreas and islet transplantation, which could lay the foundation for its future clinical application.