| First Author | Vigueira PA | Year | 2014 |
| Journal | Cell Rep | Volume | 7 |
| Issue | 6 | Pages | 2042-2053 |
| PubMed ID | 24910426 | Mgi Jnum | J:211781 |
| Mgi Id | MGI:5576400 | Doi | 10.1016/j.celrep.2014.05.017 |
| Citation | Vigueira PA, et al. (2014) Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose-stimulated insulin secretion. Cell Rep 7(6):2042-53 |
| abstractText | 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(Delta16)) 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(Delta16) mice. Additionally, compared with wild-type controls, Mpc2(Delta16) 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 beta cell glucose sensing. |
