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Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

التفاصيل البيبلوغرافية
العنوان: Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.
المؤلفون: Gray LR; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Sultana MR; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Rauckhorst AJ; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Oonthonpan L; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Tompkins SC; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Sharma A; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Fu X; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Miao R; Metabolomics Core Research Facility, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Pewa AD; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Brown KS; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Lane EE; Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of the Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Dohlman A; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Zepeda-Orozco D; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of the Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Xie J; Cell Signaling Technology, Inc., Danvers, MA 01923, USA., Rutter J; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Norris AW; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of the Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Cox JE; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; Metabolomics Core Research Facility, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Burgess SC; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Potthoff MJ; Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of the Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA., Taylor EB; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Fraternal Order of the Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA; Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52240, USA. Electronic address: eric-taylor@uiowa.edu.
المصدر: Cell metabolism [Cell Metab] 2015 Oct 06; Vol. 22 (4), pp. 669-81. Date of Electronic Publication: 2015 Sep 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press, c2005-
مواضيع طبية MeSH: Glucose/*metabolism , Mitochondria, Liver/*enzymology , Proprotein Convertase 1/*metabolism, Acrylates/pharmacology ; Animals ; Cells, Cultured ; Citric Acid Cycle/drug effects ; Diet, High-Fat ; Gluconeogenesis/drug effects ; Glutamine/metabolism ; Glycogen/analysis ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Hyperglycemia/metabolism ; Hyperglycemia/prevention & control ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/etiology ; Obesity/metabolism ; Proprotein Convertase 1/deficiency ; Proprotein Convertase 1/genetics ; Proprotein Convertase 2/antagonists & inhibitors ; Proprotein Convertase 2/genetics ; Proprotein Convertase 2/metabolism ; Pyruvic Acid/metabolism ; Triglycerides/analysis
مستخلص: Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
التعليقات: Comment in: Nat Rev Endocrinol. 2015 Nov;11(11):629. (PMID: 26391977)
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معلومات مُعتمدة: R00 AR059190 United States AR NIAMS NIH HHS; R24 DK096518 United States DK NIDDK NIH HHS; R01 DK104998 United States DK NIDDK NIH HHS; R01 DK078184 United States DK NIDDK NIH HHS; T32 HL007638 United States HL NHLBI NIH HHS; T32 HL007121 United States HL NHLBI NIH HHS; P30 CA086862 United States CA NCI NIH HHS; P01 DK058398 United States DK NIDDK NIH HHS; P30CA086862 United States CA NCI NIH HHS; T32 CA078586 United States CA NCI NIH HHS; F32 DK101183 United States DK NIDDK NIH HHS; T32 GM007337 United States GM NIGMS NIH HHS; R01 GM094232 United States GM NIGMS NIH HHS; GM007337 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (Acrylates)
0 (Triglycerides)
0RH81L854J (Glutamine)
56396-35-1 (2-cyano-3-(1-phenylindol-3-yl)acrylate)
8558G7RUTR (Pyruvic Acid)
9005-79-2 (Glycogen)
EC 3.4.21.93 (Pcsk1 protein, mouse)
EC 3.4.21.93 (Proprotein Convertase 1)
EC 3.4.21.94 (Pcsk2 protein, mouse)
EC 3.4.21.94 (Proprotein Convertase 2)
IY9XDZ35W2 (Glucose)
تواريخ الأحداث: Date Created: 20150908 Date Completed: 20160729 Latest Revision: 20220318
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4754674
DOI: 10.1016/j.cmet.2015.07.027
PMID: 26344103
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-7420
DOI:10.1016/j.cmet.2015.07.027