The somatostatin receptor in human pancreatic β-cells.

The peptide hormone somatostatin (SST) is produced in the brain, the gut, and in δ-cells in pancreatic islets of Langerhans. SST secretion from δ-cells is stimulated by glucose, amino acids, and glucagon-like peptide-1. Exogenous SST strongly inhibits the secretion of the blood glucose-regulating hormones insulin and glucagon from pancreatic β-cells and α-cells, respectively. Endogenous SST secreted from δ-cells is a paracrine regulator of insulin and glucagon secretion, although the exact physiological significance of this regulation is unclear. Secreted SST binds to specific receptors (SSTRs), which are coupled to Gi/o proteins. In both β- and α-cells, activation of SSTRs suppresses hormone secretion by reducing cAMP levels, inhibiting electrical activity, decreasing Ca²⁺ influx through voltage-gated Ca²⁺ channels and directly reducing exocytosis in a Ca²⁺ and cAMP-independent manner. In rodents, β-cells express predominantly SSTR5, whereas α-cells express SSTR2. In human islets, SSTR2 is the dominant receptor in both β- and α-cells, but other isoforms also contribute to the SST effects. Evidence from rodent models suggests that SST secretion from δ-cells is dysregulated in diabetes mellitus, which may contribute to the metabolic disturbances in this disease. SST analogues are currently used for the treatment of hyperinsulinism and other endocrine disorders, including acromegaly and Cushing's syndrome.