Abstract

The former specific aims were: 1) To test the hypothesis that the increase in malonyl-CoA caused by an excess of glucose is related to cytosolic citrate. 2) To explore the possibility that other kinases interact with AMPK in regulating ACC activity and fatty acid oxidation in muscle. 3) To extend preliminary observations suggesting that malonyl-CoA decarboxylase is regulated by phosphorylation and that its activity is increased in muscle contraction. The subcellular distribution of MCD and whether its activity is regulated by AMPK or other kinases activated by muscle contraction will be assessed. 4) To determine if the high concentration of malonyl-CoA that has been found in muscle mitochondria is due to transport from the cytosol or de novo synthesis. 5) To evaluate whether alterations in one or more of the mechanisms we have defined can explain elevated levels of malonyl-CoA in muscle in situations for which no definitive explanation currently exists such as the Dahl-salt-sensitive rat. The investigators have responded to the reviewer's

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK019514-23
Application #
6624828
Study Section
Metabolism Study Section (MET)
Program Officer
Laughlin, Maren R
Project Start
1979-06-01
Project End
2005-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
23
Fiscal Year
2003
Total Cost
$306,862
Indirect Cost

  Institution

Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Mugabo, Yves; Zhao, Shangang; Seifried, Annegrit et al. (2016) Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic ?-cells and hepatocytes. Proc Natl Acad Sci U S A 113:E430-9
Weikel, Karen A; Cacicedo, José M; Ruderman, Neil B et al. (2016) Knockdown of GSK3? increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells. Biosci Rep 36:
Coughlan, Kimberly A; Valentine, Rudy J; Sudit, Bella S et al. (2016) PKD1 Inhibits AMPK?2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells. J Biol Chem 291:5664-75
Weikel, Karen A; Ruderman, Neil B; Cacicedo, José M (2016) Unraveling the actions of AMP-activated protein kinase in metabolic diseases: Systemic to molecular insights. Metabolism 65:634-45
Pepin, Émilie; Al-Mass, Anfal; Attané, Camille et al. (2016) Pancreatic ?-Cell Dysfunction in Diet-Induced Obese Mice: Roles of AMP-Kinase, Protein Kinase C?, Mitochondrial and Cholesterol Metabolism, and Alterations in Gene Expression. PLoS One 11:e0153017
Xu, X Julia; Apovian, Caroline; Hess, Donald et al. (2015) Improved Insulin Sensitivity 3 Months After RYGB Surgery Is Associated With Increased Subcutaneous Adipose Tissue AMPK Activity and Decreased Oxidative Stress. Diabetes 64:3155-9
Nolan, Christopher J; Ruderman, Neil B; Kahn, Steven E et al. (2015) Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes. Diabetes 64:673-86
Coughlan, Kimberly A; Balon, Thomas W; Valentine, Rudy J et al. (2015) Nutrient Excess and AMPK Downregulation in Incubated Skeletal Muscle and Muscle of Glucose Infused Rats. PLoS One 10:e0127388
Doménech, Elena; Maestre, Carolina; Esteban-Martínez, Lorena et al. (2015) AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nat Cell Biol 17:1304-16
Martínez de Morentin, Pablo B; Lage, Ricardo; González-García, Ismael et al. (2015) Pregnancy induces resistance to the anorectic effect of hypothalamic malonyl-CoA and the thermogenic effect of hypothalamic AMPK inhibition in female rats. Endocrinology 156:947-60

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