Nitric oxide and neuronal and pancreatic beta cell death

Abstract

Neural cells are found in all organs of the body and play an important role in the maintenance of the internal milieu. The pancreatic beta cell is the most numerous cell types in the endocrine pancreas. It is particularly important because of its role in insulin secretion, a crucial hormone in glucose metabolism. In view of this, the significance of the survival of neural and pancreatic beta cell cannot be over emphasised. Neural and pancreatic beta cell death occurs in a variety of ways. The destruction of neural cells can be induced with (1) free radicals (H(2)O(2), O(2)(-)(,) HO(-)) and nitric oxide; (2) Cytokines (tumour necrosis factor, interleukin-1 beta, interferon-gamma); (3) Glutamate; (4) Amphetamine analog (Ecstasy); (5) S100 protein; (6) Ammonia; (7) Iron ions; (8) Resins, e.g. methylmethycrylate. Pancreatic beta cell can be destroyed by (1) free radicals (H(2)O(2), O(2)(-)(,) HO(-)) and nitric oxide; (2) Cytokines (tumour necrosis factor, interleukin-1 beta, interferon-gamma); (3) alkylating agents (streptozotocin, alloxan, N-methyl-nitrosourea N-ethyl-N-nitrosourea, Methylmethanesulphonate and ethylmethanesulphonate); (4) hyperglycaemia; (5) islet amyloid poplypeptide; and (6) Inositol Monophosphate dehydrogenase inhibitors. There is enough evidence that most of these agents involved in neural and pancreatic beta cell death exert their toxic effects through the nitric oxide pathway. Neuroprotective agents include vitamin B12 analogs and alpha-tocopherol, NOS inhibitors, antioxidants (e.g. glutathione, superoxide dismutase), metals like cobalt, neurotrophic receptors (Akt kinase) and growth factors. The pancreatic beta cell death induced by these toxic agents can be prevented and or delayed by nicotinamide (vitamin B3), heat shock, copper, alpha-tocopherol (vitamin E), succinic acid, dihydroxylipoic acid, fusidic acid, glucocorticoids, cyclosporin A, growth factors and gene therapy.