Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity.

Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.