ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This experimental study quantified the physiological contribution of pancreatic δ-cells to the glycemic set point. It used 3 orthogonal mouse models to remove somatostatin (SST) signalling within the pancreas or transplanted islets. Ablation of δ-cells or SST decreased the glycemic set point, and the glucose threshold for insulin response from β-cells, leading to increased insulin secretion to the same glucose challenge.

The roles of β- and α-cells in regulating glucose homeostasis is well defined, whereby insulin secreted by β-cells regulates glucose levels primarily in the prandial status, and glucagon produced by α-cells controls glucose levels in the fasting status (1). This study clarifies the role of the third major cell type in pancreatic islets, δ-cells, and the related production of SST, in regulating the glycemic set point and β-cell insulin production.

The study used a mouse model of inducible ablation of SST-producing cells via administration of diphtheria toxin, which ablated pancreatic δ-cells but not other SST-producing cells. This led to a persistent decrease in glucose levels and glycemic set point as well as improved glucose tolerance and plasma insulin levels. Calcium imaging, used as a proxy for insulin secretion, showed that SST changed the threshold for insulin secretion. Whereas in mice with intact δ-cells, most β-cells showed a change in calcium signalling at glucose concentrations of 8–9 mmol, in mice with ablated δ-cells, most β-cells responded at 7–8 mmol.

These findings suggest that δ-cells shift the glucose threshold for insulin secretion through local inhibitory interactions with β-cells. This δ-cell mediated mechanism may safeguard against inappropriate and acutely dangerous hyperinsulinemic hypoglycemia.

These experiments were conducted on healthy mouse models and the implications in the context of other diabetes-prone models is unclear. Further studies should clarify the potential implications in the context of type 1 or type 2 diabetes management.

References: 1. Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp Mol Med. 2016;48(3):e219.