1759-P: Delta Cell Potentiates Secretion of Insulin and Glucagon in a Novel Model of Islet Paracrine Interactions

The islet δ-cell secretes SST, a peptide which is a strong paracrine inhibitor of insulin and glucagon secretion. It is conceivable, that the δ-cell, as an inner homeostatic element in the islet to prevent the spillover of both hormones.There are insufficient data to ascertain the intraislet mechanisms governing the δ-cell activity and its impact on the islet secretory output. We aimed to 1) study the correlation between insulin and somatostatin secretion in human islets from healthy and diabetic donors as well as mice fed control or high fat diet; and 2) mechanistic studies to dissect the role the δ-cell plays in the islet secretory output using transgenic mouse models. Our data allows us to propose a revised model of intraislet paracrine interactions that challenges the view of the δ-cell solely as a suppressive element on islet secretion. We propose that δ-cells paradoxically may enhance the secretion of both glucoregulatory hormones through short and sharp events inhibition driven by its pulsatile secretion, besides its canonical inhibiting role. δ-cell activation leads to peaks of somatostatin secretion appears to cause asynchronous off-responses secretory responses of neighboring α- and β- cells after somatostatin falloff, prompting a net increase in the magnitude of insulin and glucagon secretions. This model provides a comprehensive explanation for our contradictory results of the effects manipulating δ-cells has on the mouse glucose metabolism, such as, the improved glucose metabolic readouts upon activation, inhibition or even ablation of the δ-cells. Our findings emphasize the importance of understanding the mechanism that link δ-cells to pathological events in the natural history of Diabetes.