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Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose

AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin sign...

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Detalles Bibliográficos
Autores principales: Tsubai, Tomomi, Noda, Yukihiro, Ito, Kazuma, Nakao, Makoto, Seino, Yusuke, Oiso, Yutaka, Hamada, Yoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121139/
https://www.ncbi.nlm.nih.gov/pubmed/27896318
http://dx.doi.org/10.1016/j.heliyon.2016.e00194
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author Tsubai, Tomomi
Noda, Yukihiro
Ito, Kazuma
Nakao, Makoto
Seino, Yusuke
Oiso, Yutaka
Hamada, Yoji
author_facet Tsubai, Tomomi
Noda, Yukihiro
Ito, Kazuma
Nakao, Makoto
Seino, Yusuke
Oiso, Yutaka
Hamada, Yoji
author_sort Tsubai, Tomomi
collection PubMed
description AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin signal transduction in adipocytes cultured under glucose-free or normal conditions. METHODS: Differentiated 3T3-L1 adipocytes were stimulated with insulin in combination with inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free or normal conditions. After 8 h of stimulation, leptin protein levels in the media and leptin mRNA expression levels in the adipocytes were measured. RESULTS: Insulin significantly increased the secretion and mRNA levels of leptin under the depletion of glucose. Glucose augmented basal leptin secretion without insulin, while glucose nullified insulin-induced leptin mRNA upregulation. The PI3K inhibitor BEZ-235, the Akt inhibitor MK-2206, and the PDE3B inhibitor cilostazol attenuated the insulin stimulation of leptin secretion, but did not suppress the insulin-induced leptin mRNA upregulation with glucose depletion. In contrast to the glucose-free condition, insulin failed to upregulate leptin mRNA in the presence of glucose. The cAMP analog dibutyryl cAMP and epinephrine decreased both leptin secretion and mRNA regardless of glucose supplementation. CONCLUSION: Insulin alone stimulates leptin secretion and elevates leptin mRNA levels via cAMP under the lack of glucose metabolism, while glucose is a significant and ambivalent effector on the insulin effects of leptin.
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spelling pubmed-51211392016-11-28 Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose Tsubai, Tomomi Noda, Yukihiro Ito, Kazuma Nakao, Makoto Seino, Yusuke Oiso, Yutaka Hamada, Yoji Heliyon Article AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin signal transduction in adipocytes cultured under glucose-free or normal conditions. METHODS: Differentiated 3T3-L1 adipocytes were stimulated with insulin in combination with inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free or normal conditions. After 8 h of stimulation, leptin protein levels in the media and leptin mRNA expression levels in the adipocytes were measured. RESULTS: Insulin significantly increased the secretion and mRNA levels of leptin under the depletion of glucose. Glucose augmented basal leptin secretion without insulin, while glucose nullified insulin-induced leptin mRNA upregulation. The PI3K inhibitor BEZ-235, the Akt inhibitor MK-2206, and the PDE3B inhibitor cilostazol attenuated the insulin stimulation of leptin secretion, but did not suppress the insulin-induced leptin mRNA upregulation with glucose depletion. In contrast to the glucose-free condition, insulin failed to upregulate leptin mRNA in the presence of glucose. The cAMP analog dibutyryl cAMP and epinephrine decreased both leptin secretion and mRNA regardless of glucose supplementation. CONCLUSION: Insulin alone stimulates leptin secretion and elevates leptin mRNA levels via cAMP under the lack of glucose metabolism, while glucose is a significant and ambivalent effector on the insulin effects of leptin. Elsevier 2016-11-16 /pmc/articles/PMC5121139/ /pubmed/27896318 http://dx.doi.org/10.1016/j.heliyon.2016.e00194 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Tsubai, Tomomi
Noda, Yukihiro
Ito, Kazuma
Nakao, Makoto
Seino, Yusuke
Oiso, Yutaka
Hamada, Yoji
Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title_full Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title_fullStr Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title_full_unstemmed Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title_short Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose
title_sort insulin elevates leptin secretion and mrna levels via cyclic amp in 3t3-l1 adipocytes deprived of glucose
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121139/
https://www.ncbi.nlm.nih.gov/pubmed/27896318
http://dx.doi.org/10.1016/j.heliyon.2016.e00194
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