2-ketoglutarate generation in pancreatic B-cell mitochondria regulates insulin secretory action of amino acids and 2-keto acids.
The various neutral amino acids and aliphatic 2-keto acids exhibit differential effects on insulin secretion. The common denominator for all these effects is the 2-ketoglutarate generation in the pancreatic B-cell mitochondria. The neutral amino acids L-leucine and L-norvaline and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, 2-ketovalerate, and 2-keto-3-methylvalerate all stimulate insulin secretion and increase 2-ketoglutarate generation in pancreatic B-cell mitochondria through activation of glutamate dehydrogenase and transamination with L-glutamate and L-glutamine, respectively. The neutral amino acids L-valine, L-norleucine, and L-alanine and the aliphatic 2-keto acids 2-ketoisovalerate and pyruvate do not stimulate insulin secretion and do not increase 2-ketoglutarate generation in pancreatic B-cell mitochondria. Inhibition of 2-keto acid induced insulin secretion by L-valine and L-isoleucine is accompanied by reduced 2-ketoglutarate generation in pancreatic B-cell mitochondria. Thus intramitochondrial 2-ketoglutarate generation in pancreatic B-cells may regulate the insulin secretory potency of amino acids and 2-keto acids.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007532:Isoleucine / Q000494:pharmacology; D007651:Keto Acids / Q000494:pharmacology*; D007656:Ketoglutaric Acids / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism*; D014633:Valine / Q000494:pharmacology
D000596:Amino Acids; D007328:Insulin; D007651:Keto Acids; D007656:Ketoglutaric Acids; D007532:Isoleucine; D014633:Valine