Targeting the insulin granule for modulation of insulin exocytosis.

Abstract The pancreatic β-cells control insulin secretion in the body to regulate glucose homeostasis and β-cell stress and dysfunction is characteristic of Type 2 Diabetes. Pharmacological targeting of the β-cell to increase insulin secretion is typically utilised, however, extended use of common drugs such as sulfonylureas are known to result in secondary failure. Moreover, there is evidence they may induce β-cell failure in the long term. Within β-cells, insulin secretory granules (ISG) serve as compartments to store, process and traffic insulin for exocytosis. There is now growing evidence that ISG exist in multiple populations, distinct in their protein composition, motility, age, and capacity for secretion. In this review, we discuss the implications of a heterogenous ISG population in β-cells and highlight the need for more understanding into how unique ISG populations may be targeted in anti-diabetic therapies.