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Cell Rep. 2014 Jun 26;7(6):2042-2053. doi: 10.1016/j.celrep.2014.05.017. Epub 2014 Jun 5.

Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose-stimulated insulin secretion.

Author information

Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Advanced Imaging Research Center and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Metabolic Solutions Development Company, Kalamazoo, MI 49007, USA.
Contributed equally


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 (Mpc2(Δ16)) 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 Mpc2(Δ16) mice. Additionally, compared with wild-type controls, Mpc2(Δ16) 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.

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