Amino Acid Sensing by the α-Cell Mitochondrial Phosphoenolpyruvate Cycle Regulates Intracellular Ca2+ Levels Without Affecting Glucagon Secretion.

ABSTRACT: Pancreatic islet α-cells are increasingly recognized as amino acid sensors for the organism. Building on our prior work in β-cells, we sought to determine whether the mitochondrial phosphoenolpyruvate (PEP) cycle is involved in α-cell amino acid sensing. Three different methods were used to probe the PEP cycle, including pyruvate kinase activators (TEPP-46), and mice with α-cell-specific deletion (KO) of pyruvate kinase M (PKM1/2-αKO) or mitochondrial PEP carboxykinase (PCK2-αKO). The mitochondrial fuel leucine, in the presence of glutamine, antagonized alanine/arginine-stimulated Ca2+ influx and glucagon secretion under hypoglycemic conditions. Both PKM1/2 and PCK2 deletion prevented leucine from closing α-cell KATP channels. The Ca2+ response to amino acids was suppressed by pyruvate kin

SUBMITTER: Jin E 

PROVIDER: S-EPMC12928745 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature