Genetic deletion of mitochondrial PEP carboxykinase (PCK2) in pancreatic α cells increases amino acid-stimulated Ca2+ influx and boosts the excitability of neighboring β-cells

Abstract

Amino acids potently stimulate glucagon secretion, but their mechanisms of action remain largely unknown. To assess the effects of individual amino acids on α-cell Ca2+, we used GcgCreERT:GCaMP6s Ca2+ reporter mice in combination with epifluorescence and light-sheet imaging to monitor the behavior of single α-cells within the intact islet. We focused on alanine, arginine, glutamine, and leucine, which have the potential to affect Ca2+ and glucagon release via their transport or metabolism. At low glucose, when β-cells are inactive, alanine and arginine provoked a sustained increase in Ca2+.