Paracrine signaling by pancreatic δ cells determines the glycemic set point in mice

Abstract

SUMMARYPancreatic islets contain several endocrine cell types that coordinate to maintain blood glucose homeostasis. While β and α cells are thought to be the main drivers of glucose homeostasis through insulin and glucagon secretion respectively, the contribution of δ cells and somatostatin (SST) secretion to establishing the glycemic set point remains unresolved. Here we remove local SST signaling from δ cells within the pancreatic islet to investigate their contribution to the glycemic set point. Our data demonstrate that ablating δ cells or SST leads to a sustained decrease in the glycemic set point. This coincides with a decreased glucose threshold for insulin response from β cells, leading to increased insulin secretion to the same glucose challenge. In contrast, α cell ablation had no effect on glycemic set point. Collectively, these data establish the physiological role of δ cells in determining the glycemic set point through their interaction with β cells.