Pancreatic beta cell death - is nitric oxide the culprit?

The pancreatic beta cell is the most numerous cell type in the endocrine pa ncreas. It is particularly important because of its role in insulin secreti on, a crucial hormone in glucose metabolism. In view of this, the significa nce of the survival of pancreatic beta cell cannot be over emphasised. Panc reatic beta cell death occurs in a variety of ways. The destruction of beta cell can be induced by 1: free radicals (H2O2, O-2(-), HO-) and nitric oxi de; 2. Cytokines (tumour necrosis factor, interleukin-1 beta, interferon-ga mma); 3: alkylating agents (streptozotocin, alloxan, N-methyl-nitrosourea N -ethyl-N-nitrosourea, Methylmethanesulphonate and ethylmethanesulphonate); 4: hyperglycaemia; 5. islet amyloid poplypeptide and 6. Inositol Monophosph ate dehydrogenase inhibitors. There is enough evidence that alkylation agen ts and cytokines exert their toxic effects on pancreatic beta cell through the nitric oxide pathway. The pancreatic beta cell death induced by these t oxic agents can be prevented and or delayed by nicotinamide (vitamin B3), h eat shock, copper, alpha-tocopherol (vitamin E), succinic acid, dihydroxyli poic acid, fusidic acid, glucocorticoids, cyclosporin A, growth factors and gene therapy.