Abstract

This proposal examines the pathway by which insulin regulates GLUT4 translocation in adipocytes. The P.I. has devised a novel method that will enable him to study the cycling of GLUT4 in these cells.
Specific aims are (1) to kinetically characterize the insulin-regulated trafficking pathway. This will be done by measuring the rate constants of endocytosis and recycling, both in the presence and absence of insulin. (2) To characterize the intracellular compartments of the insulin-regulated trafficking pathway using quantitative fluorescence microscopy. The relationship with the general recycling pathway will be determined. (3) To identify the proteins of the insulin-regulated recycling compartment using HRP ablation. Novel IRC proteins will be identified. (4) To identify the trafficking motifs of the cytoplasmic domains of vp165.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052852-02
Application #
2770641
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Haft, Carol R
Project Start
1997-09-01
Project End
2001-08-31
Budget Start
1998-09-17
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Haeusler, Rebecca A; McGraw, Timothy E; Accili, Domenico (2018) Biochemical and cellular properties of insulin receptor signalling. Nat Rev Mol Cell Biol 19:31-44
Waldhart, Althea N; Dykstra, Holly; Peck, Anderson S et al. (2017) Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose in Response to Insulin. Cell Rep 19:2005-2013
Brumfield, Alexandria; Chaudhary, Natasha; McGraw, Timothy E (2017) Secretion of Adipsin as an Assay to Measure Flux from the Endoplasmic Reticulum (ER). Bio Protoc 7:
Vazirani, Reema P; Verma, Akanksha; Sadacca, L Amanda et al. (2016) Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance. Diabetes 65:1577-89
Bruno, Joanne; Brumfield, Alexandria; Chaudhary, Natasha et al. (2016) SEC16A is a RAB10 effector required for insulin-stimulated GLUT4 trafficking in adipocytes. J Cell Biol 214:61-76
Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee et al. (2016) Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes. Cell Rep 17:3305-3318
Kajno, Esi; McGraw, Timothy E; Gonzalez, Eva (2015) Development of a new model system to dissect isoform specific Akt signalling in adipocytes. Biochem J 468:425-34
Antonescu, Costin N; McGraw, Timothy E; Klip, Amira (2014) Reciprocal regulation of endocytosis and metabolism. Cold Spring Harb Perspect Biol 6:a016964
Sadacca, L Amanda; Bruno, Joanne; Wen, Jennifer et al. (2013) Specialized sorting of GLUT4 and its recruitment to the cell surface are independently regulated by distinct Rabs. Mol Biol Cell 24:2544-57
Wu, Ning; Zheng, Bin; Shaywitz, Adam et al. (2013) AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol Cell 49:1167-75

Showing the most recent 10 out of 38 publications