Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion

Patrick A. Vigueira, Kyle S. McCommis, George G. Schweitzer, Maria S. Remedi, Kari T. Chambers, Xiaorong Fu, William G. McDonald, Serena L. Cole, Jerry R. Colca, Rolf F. Kletzien, Shawn C. Burgess, Brian N. Finck

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Carrier-facilitated pyruvate transport across the inner mitochondrial membrane plays an essential role in anabolic and catabolic intermediary metabolism. Mitochondrial pyruvate carrier 2 (Mpc2) is believed to be a component of the complex that facilitates mitochondrial pyruvate import. Complete MPC2 deficiency resulted in embryonic lethality in mice. However, a second mouse line expressing an N-terminal truncated MPC2 protein (Mpc2δ16) was viable but exhibited a reduced capacity for mitochondrial pyruvate oxidation. Metabolic studies demonstrated exaggerated blood lactate concentrations after pyruvate, glucose, or insulin challenge in Mpc2δ16 mice. Additionally, compared with wild-type controls, Mpc2δ16 mice exhibited normal insulin sensitivity but elevated blood glucose after bolus pyruvate or glucose injection. This was attributable to reduced glucose-stimulated insulin secretion and was corrected by sulfonylurea KATP channel inhibitor administration. Collectively, these data are consistent with a role for MPC2 in mitochondrial pyruvate import and suggest that Mpc2 deficiency results in defective pancreatic β cell glucose sensing.

Original languageEnglish (US)
Pages (from-to)2042-2053
Number of pages12
JournalCell Reports
Volume7
Issue number6
DOIs
StatePublished - Jun 26 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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