Role of histamine H3 receptor in glucagon-secreting αTC1.6 cells

•Histamine H3 receptor is expressed in pancreatic α-cells.•Histamine H3 receptor negatively regulates glucagon secretion from αTC1.6 cells.•Immepip, a selective H3 receptor agonist, decreases serum glucagon concentration in rats.

Pancreatic α-cells secrete glucagon to maintain energy homeostasis. Although histamine has an important role in energy homeostasis, the expression and function of histamine receptors in pancreatic α-cells remains unknown. We found that the histamine H3 receptor (H3R) was expressed in mouse pancreatic α-cells and αTC1.6 cells, a mouse pancreatic α-cell line. H3R inhibited glucagon secretion from αTC1.6 cells by inhibiting an increase in intracellular Ca2+ concentration. We also found that immepip, a selective H3R agonist, decreased serum glucagon concentration in rats. These results suggest that H3R modulates glucagon secretion from pancreatic α-cells.