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Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes.
Endocrine. 2016 Jan; 51(1):174-84.E

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.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. semmarut@koto.kpu-m.ac.jp.Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.Radioisotope Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.Institute of Bio-Response Informatics, Kyoto, Japan.Institute of Bio-Response Informatics, Kyoto, Japan.Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26100787

Citation

Mitsuhashi, Kazuteru, et al. "Testosterone Stimulates Glucose Uptake and GLUT4 Translocation Through LKB1/AMPK Signaling in 3T3-L1 Adipocytes." Endocrine, vol. 51, no. 1, 2016, pp. 174-84.
Mitsuhashi K, Senmaru T, Fukuda T, et al. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine. 2016;51(1):174-84.
Mitsuhashi, K., Senmaru, T., Fukuda, T., Yamazaki, M., Shinomiya, K., Ueno, M., Kinoshita, S., Kitawaki, J., Katsuyama, M., Tsujikawa, M., Obayashi, H., Nakamura, N., & Fukui, M. (2016). Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine, 51(1), 174-84. https://doi.org/10.1007/s12020-015-0666-y
Mitsuhashi K, et al. Testosterone Stimulates Glucose Uptake and GLUT4 Translocation Through LKB1/AMPK Signaling in 3T3-L1 Adipocytes. Endocrine. 2016;51(1):174-84. PubMed PMID: 26100787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. AU - Mitsuhashi,Kazuteru, AU - Senmaru,Takafumi, AU - Fukuda,Takuya, AU - Yamazaki,Masahiro, AU - Shinomiya,Katsuhiko, AU - Ueno,Morio, AU - Kinoshita,Shigeru, AU - Kitawaki,Jo, AU - Katsuyama,Masato, AU - Tsujikawa,Muneo, AU - Obayashi,Hiroshi, AU - Nakamura,Naoto, AU - Fukui,Michiaki, Y1 - 2015/06/23/ PY - 2015/02/25/received PY - 2015/06/12/accepted PY - 2015/6/24/entrez PY - 2015/6/24/pubmed PY - 2016/10/26/medline KW - AMPK signaling KW - GLUT4 translocation KW - Glucose uptake KW - Non-genomic action KW - Testosterone SP - 174 EP - 84 JF - Endocrine JO - Endocrine VL - 51 IS - 1 N2 - 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. SN - 1559-0100 UR - https://www.unboundmedicine.com/medline/citation/26100787/Testosterone_stimulates_glucose_uptake_and_GLUT4_translocation_through_LKB1/AMPK_signaling_in_3T3_L1_adipocytes_ L2 - https://dx.doi.org/10.1007/s12020-015-0666-y DB - PRIME DP - Unbound Medicine ER -