Testosterone Stimulates Glucose Uptake and GLUT4 Translocation Through LKB1/AMPK Signaling in 3T3-L1 Adipocytes

Overview

Journal Endocrine

Specialty Endocrinology

Date 2015 Jun 24

PMID 26100787

Citations 31

Authors

Kazuteru Mitsuhashi

Takafumi Senmaru

Takuya Fukuda

Masahiro Yamazaki

Katsuhiko Shinomiya

Morio Ueno

Shigeru Kinoshita

Jo Kitawaki

Masato Katsuyama

Muneo Tsujikawa

Hiroshi Obayashi

Naoto Nakamura

Michiaki Fukui

Affiliations

Soon will be listed here.

Abstract

Decreases in serum testosterone concentrations in aging men are associated with metabolic disorders. Testosterone has been reported to increase GLUT4-dependent glucose uptake in skeletal muscle cells and cardiomyocytes. However, studies on glucose uptake occurring in response to testosterone stimulation in adipocytes are currently not available. This study was designed to determine the effects of testosterone on glucose uptake in adipocytes. Glucose uptake was assessed with 2-[(3)H] deoxyglucose in 3T3-L1 adipocytes. GLUT4 translocation was evaluated in plasma membrane (PM) sheets and PM fractions by immunofluorescence and immunoblotting, respectively. Activation of GLUT4 translocation-related protein kinases, including Akt, AMPK, LKB1, CaMKI, CaMKII, and Cbl was followed by immunoblotting. Expression levels of androgen receptor (AR) mRNA and AR translocation to the PM were assessed by real-time RT-PCR and immunoblotting, respectively. The results showed that both high-dose (100 nM) testosterone and testosterone-BSA increased glucose uptake and GLUT4 translocation to the PM, independently of the intracellular AR. Testosterone and testosterone-BSA stimulated the phosphorylation of AMPK, LKB1, and CaMKII. The knockdown of LKB1 by siRNA attenuated testosterone- and testosterone-BSA-stimulated AMPK phosphorylation and glucose uptake. These results indicate that high-dose testosterone and testosterone-BSA increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes by inducing the LKB1/AMPK signaling pathway.

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