Pancreatic beta cell death - Is nitric oxide the culprit?

The pancreatic beta cell is the most numerous cell type 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 pancreatic beta cell cannot be over emphasised. Pancreatic beta cell death occurs in a variety of ways. The destruction of beta cell can be induced by 1: free radicals (H₂O₂, O₂^-, 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 alkylation agents and cytokines exert their toxic effects on pancreatic beta cell through the nitric oxide pathway. 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.