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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

1
Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Advanced Imaging Research Center and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4
Metabolic Solutions Development Company, Kalamazoo, MI 49007, USA.
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Contributed equally

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 (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.

PMID:
24910426
PMCID:
PMC4074444
DOI:
10.1016/j.celrep.2014.05.017
[Indexed for MEDLINE]
Free PMC Article

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