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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844016307009 |
| _version_ | 1818864324631855104 |
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| author | Tomomi Tsubai Yukihiro Noda Kazuma Ito Makoto Nakao Yusuke Seino Yutaka Oiso Yoji Hamada |
| author_facet | Tomomi Tsubai Yukihiro Noda Kazuma Ito Makoto Nakao Yusuke Seino Yutaka Oiso Yoji Hamada |
| author_sort | Tomomi Tsubai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T10:29:51Z |
| format | Article |
| id | doaj.art-0028358403de477183808d469a6f1972 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-19T10:29:51Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-0028358403de477183808d469a6f19722022-12-21T20:25:46ZengElsevierHeliyon2405-84402016-11-0121110.1016/j.heliyon.2016.e00194Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucoseTomomi Tsubai0Yukihiro Noda1Kazuma Ito2Makoto Nakao3Yusuke Seino4Yutaka Oiso5Yoji Hamada6College of Pharmacy, Kinjo Gakuin University; Omori 2-1723, Moriyama-ku, Nagoya 463-8521, JapanDivision of Clinical Science and Neuropsychopharmacology, Graduate School and Faculty of Pharmacy, Meijo University; 150, Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDivision of Clinical Science and Neuropsychopharmacology, Graduate School and Faculty of Pharmacy, Meijo University; 150, Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanCollege of Pharmacy, Kinjo Gakuin University; Omori 2-1723, Moriyama-ku, Nagoya 463-8521, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine; 65, Tsuruma-cho, Showa-ku, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine; 65, Tsuruma-cho, Showa-ku, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine; 65, Tsuruma-cho, Showa-ku, Nagoya 466-8560, JapanAims: 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.http://www.sciencedirect.com/science/article/pii/S2405844016307009MedicineEndocrinology |
| spellingShingle | Tomomi Tsubai Yukihiro Noda Kazuma Ito Makoto Nakao Yusuke Seino Yutaka Oiso Yoji Hamada Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose Heliyon Medicine Endocrinology |
| 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 | Medicine Endocrinology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844016307009 |
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