Transplantation of insulin-secreting tissues

Abstract

The past 15 years have brought the unwelcome realisation that parenteral insulin and oral hypoglycaemic agents have failed to prevent the macro-and microvascular complications associated with diabetes mellitus. The inability of current therapeutic approaches to alter significantly the morbidity and mortality caused by the vascular disease seen in diabetic patients has been measured by the University Group Diabetes Program1. Although discussion of the exact nature of the biochemical lesion in diabetes has led to great controversy, it is reasonably well accepted that at least one basic defect resides in the beta cell of the islets of Langerhans2. Thus, all forms of diabetes are characterised by a 'relative' deficiency of circulating insulin3. Detailed studies of insulin secretion in normal and diabetic subjects indicate that the cells are sluggish in their response to glucose stimulation2. The failure of exogenous agents - for example, insulin, and the oral hypoglycaemic agents - to effect a rigorous control of blood sugar from minute to minute may explain the failure of such agents to prevent the complications of diabetes. As the basic defect probably lies in the beta cells, it has been postulated that successful transplantation of normal beta cells into the diabetic patient may prevent the development of vascular complications in the brain, eye, kidney, peripheral nervous system, and other tissues. Since 1965, the feasibility of beta cell transplantation, as intact isolated islets of Langerhans, in fragments of pancreas or in the whole pancreas, has been actively investigated. The majority of experiments have involved animals made diabetic by the administration of special beta cell poisons (alloxan and streptozotocin) as recipients of islet-containing tissue. A review is presented.