Future alternative therapies in a quest to halt aberrations in diabetes mellitus

Under normal physiological conditions, euglycaemia is maintained principally by the homeostatic balance of insulin and glucagon which are secreted from the pancreas. In both type 1 and type 2 diabetes mellitus there is a substantial and chronic increase in the circulating glucose concentration. This elevation in glucose levels is accompanied by a plethora of other biochemical disturbances, including disruption of carbohydrate, fat and protein metabolism. Clinical manifestations of diabetes, which arise from the metabolic disturbances vary between individuals but are often a serious threat to quality and length of life. Pancreas transplantation (Tx) and islet modifications are methods used to restore endogenous insulin secretion in insulin-dependent diabetic patients. In order for this to be achieved successfully, however, some of the problems such as hyperglycemia states (>150 mg/dl), which may harm pancreatic graft beta cells, immunorejection, the effects of immunosuppression, for example, must be overcome. Considering these problems, therefore, it seems logical that the replacement of the islet tissue itself, either by transplanting a vascularised pancreatic allograft or by transplanting modified pancreatic islet cells, provides a better alternative therapeutic approach than simply replacing insulin that has been lost. This review will show the recent development in the use of pancreatic islets and their modification in a quest to halt the aberrations seen in diabetes mellitus.