EASD/JDRF Symposium
Beta cell imaging and regeneration - between the hype and the hope
Beta cell regeneration: How good is good enough?

Both major forms of diabetes arise through an absolute (type 1) or a relative (type 2) decrease in beta cell mass. Current therapy for diabetes has improved greatly in recent years, with insulin replacement therapy combined with glucose monitoring and/or oral hypoglycaemic agents to enhance beta cell function and improve insulin sensitivity allowing for closer glucose control than was previously possible. However, control is not perfect and there is no cure for diabetes today aside from the few patients with long-term beta cell function after pancreas or (even fewer) after islet transplantation. Beta cell regeneration would provide the cure for type 1 diabetes and if combined with successful reversal of insulin resistance, could also possibly cure type 2 diabetes.

Despite extraordinary advances in our understanding of beta cell development, function and survival in health and disease, and the feeling that we are tantalizingly close to the goal of beta cell replacement therapy, the challenge is still huge. The last mile may be the toughest.

The beta cell has evolved to respond to minute-by-minute changes in metabolic status and notably glycaemia, with appropriate changes in insulin secretion. The microenvironment of the beta cell plays a critical role in its function and survival. This includes both the metabolic environment (notably glucose and fatty acids) as well as the physical environment encompassing vasculature, cell-cell and cell-matrix interactions: changes to this microenvironment impact profoundly on beta cell function and survival.

Regardless of the source or origin of any replacement or regenerated insulin-producing cell, it will thus be necessary to ensure that insulin secretion is as well regulated as that from a natural beta cell. For this, the cell will need to be fully differentiated and in an appropriate microenvironment. This is the ultimate challenge that must be met. We now understand many of the events leading to regulated insulin secretion from beta cells and these will be described. They depend upon expression of a unique panel of genes in beta cells. Contemporary methods of gene analysis now allow for identification of all such genes needed for fully differentiated function of the beta cell and this will in turn allow for complete characterization of any replacement o regenerating cells.

Aside from meeting the stringent test of behaving as closely as possible to their natural counterpart in terms of regulated insulin secretion, new beta cells must also be protected from destruction following implantation in a diabetic environment and could possibly be engineered with improved survival skills: the delicate balance between differentiated function and susceptibility to stress will be an important confounding factor.