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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Jun 8

PMID 28591573

Citations 121

Authors

Althea N Waldhart

Holly Dykstra

Anderson S Peck

Elissa A Boguslawski

Zachary B Madaj

Jennifer Wen

Kelsey Veldkamp

Matthew Hollowell

Bin Zheng

Lewis C Cantley

Timothy E McGraw

Ning Wu

Affiliations

Soon will be listed here.

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.

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