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PMID: 28591573 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose in Response to Insulin.

Cell reports ·Vol. 19 ·No. 10 ·2017-00-06 ·Pages 2005-2013

Waldhart AN, Dykstra H, Peck AS, Boguslawski EA, Madaj ZB, Wen J, Veldkamp K, Hollowell M, Zheng B, Cantley LC, McGraw TE, Wu N

Abstract

Growth factors, such as insulin, can induce both acute and long-term glucose uptake into cells. Apart from the rapid, insulin-induced fusion of glucose transporter (GLUT)4 storage vesicles with the cell surface that occurs in muscle and adipose tissues, the mechanism behind acute induction has been unclear in other systems. Thioredoxin interacting protein (TXNIP) has been shown to be a negative regulator of cellular glucose uptake. TXNIP is transcriptionally induced by glucose and reduces glucose influx by promoting GLUT1 endocytosis. Here, we report that TXNIP is a direct substrate of protein kinase B (AKT) and is responsible for mediating AKT-dependent acute glucose influx after growth factor stimulation. Furthermore, TXNIP functions as an adaptor for the basal endocytosis of GLUT4 in vivo, its absence allows excess glucose uptake in muscle and adipose tissues, causing hypoglycemia during fasting. Altogether, TXNIP serves as a key node of signal regulation and response for modulating glucose influx through GLUT1 and GLUT4.

Keywords
AKT GLUT4 TXNIP glucose insulin
MeSH Terms
3T3-L1 Cells Adipose Tissue/metabolism Animals Carrier Proteins/genetics,metabolism Endocytosis Glucose/metabolism Glucose Transporter Type 1/genetics,metabolism Glucose Transporter Type 4/genetics,metabolism Insulin/metabolism Mice Mice, Transgenic Muscle, Skeletal/metabolism Proto-Oncogene Proteins c-akt/genetics,metabolism Signal Transduction Thioredoxins/genetics,metabolism
Chemicals
Carrier Proteins Glucose Transporter Type 1 Glucose Transporter Type 4 Insulin Slc2a1 protein, mouse Slc2a4 protein, mouse Txnip protein, mouse Thioredoxins Proto-Oncogene Proteins c-akt Glucose
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Waldhart Althea N
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Dykstra Holly
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Peck Anderson S
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Boguslawski Elissa A
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Madaj Zachary B
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Wen Jennifer
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10065, USA.
Veldkamp Kelsey
Calvin College, Grand Rapids, MI 49546, USA.
Hollowell Matthew
Calvin College, Grand Rapids, MI 49546, USA.
Zheng Bin
Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA.
Cantley Lewis C
The Sandra and Edward Meyer Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA.
McGraw Timothy E
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10065, USA.
Wu Ning
Van Andel Research Institute, Grand Rapids, MI 49503, USA. Electronic address: [email protected].
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2017.05.041
Email
[email protected]
Published
2017-00-06
Pages
2005-2013
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC5603216
Subset
IM
Grants
NCI NIH HHS · P01 CA120964 · United States
NIDDK NIH HHS · R01 DK052852 · United States
NIGMS NIH HHS · R01 GM041890 · United States
NIDDK NIH HHS · R56 DK052852 · United States
NCI NIH HHS · R35 CA197588 · United States
NIDDK NIH HHS · P30 DK020541 · United States
External Links
PubMed source DOI: 10.1016/j.celrep.2017.05.041 PMC Full Text View journal details
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