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Cell Rep. 2017 Jun 6;19(10):2005-2013. doi: 10.1016/j.celrep.2017.05.041.

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

Author information

1
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
2
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10065, USA.
3
Calvin College, Grand Rapids, MI 49546, USA.
4
Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA.
5
The Sandra and Edward Meyer Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA.
6
Van Andel Research Institute, Grand Rapids, MI 49503, USA. Electronic address: ning.wu@vai.org.

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

PMID:
28591573
PMCID:
PMC5603216
DOI:
10.1016/j.celrep.2017.05.041
[Indexed for MEDLINE]
Free PMC Article

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