Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway
Background : The acute glucose fluctuations in diabetes can be a risk factor of cardiovascular events. Nonetheless, the mechanism of action of intermittent hyperglycemia on the proliferation of vascular smooth muscle cells (VSMCs) is poorly understood. We compared the effects of exposure to constant...
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| Format: | Article |
| Language: | English |
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Korea Geriatrics Society
2017-09-01
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| Series: | Annals of Geriatric Medicine and Research |
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| Online Access: | http://www.e-agmr.org/journal/view.html?doi=10.4235/agmr.2017.21.3.131 |
| _version_ | 1811239688801878016 |
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| author | Sung Hoon Yu Hyung Joon Yoo Dong Hyun Kang Shin Je Moon Jae Myung Yu |
| author_facet | Sung Hoon Yu Hyung Joon Yoo Dong Hyun Kang Shin Je Moon Jae Myung Yu |
| author_sort | Sung Hoon Yu |
| collection | DOAJ |
| description | Background : The acute glucose fluctuations in diabetes can be a risk factor of cardiovascular events. Nonetheless, the mechanism of action of intermittent hyperglycemia on the proliferation of vascular smooth muscle cells (VSMCs) is poorly understood. We compared the effects of exposure to constant and intermittent hyperglycemia on in vitro proliferation of aortic VSMCs from obese diabetic rats. Methods : VSMCs from Otsuka Long-Evans Tokushima Fatty (OLETF) rats were incubated for 72 hours with different glucose concentrations: a constant normal-glucose medium (4.8 mM), constant high-glucose medium (24.5 mM), normal- and high-glucose media alternating every 12 hours, and mannose (12.0 mM; an osmotic control for high glucose levels). The proliferation of VSMCs was analyzed by a 3-[4,5-dimethylthiazol-2-yl]-diphenyltetrazolium bromide (MTT) assay. The molecular mechanism (including phospho-p44/42 mitogen-activated protein kinase [MAPK], mitogen-activated protein kinase kinase-1/2 (MEK1/2), Protein kinase B (Akt), and the apoptosis pathway) was then studied. Results : We detected enhanced proliferation of VSMCs incubated with the constant or intermittent high-glucose medium using the MTT assay (p<0.05). The proliferation of VSMCs was more pronounced in the intermittent high-glucose environment than at a constant high glucose concentration. In western blot analysis, treatment with the constant high-glucose medium for 72 hours increased phospho-p44/42 MAPK and phospho-MEK1/2 expression as compared to treatment with the normal-glucose medium. These effects were further enhanced by the intermittent high glucose concentration. Akt and phospho-Akt were not affected by hypergly cemia. In the apoptotic pathway, Bcl-xL, phospho-Bad, and caspase-3 were not affected by hyperglycemia for 72 hours. Conclusion : Hyperglycemia increased the proliferation of VSMCs from OLETF rats via the MAPK pathway. These effects were further enhanced by intermittent exposure to the high glucose concentration. |
| first_indexed | 2024-04-12T13:05:30Z |
| format | Article |
| id | doaj.art-1883aae79a8c4059bf35136750a50b77 |
| institution | Directory Open Access Journal |
| issn | 2508-4798 |
| language | English |
| last_indexed | 2024-04-12T13:05:30Z |
| publishDate | 2017-09-01 |
| publisher | Korea Geriatrics Society |
| record_format | Article |
| series | Annals of Geriatric Medicine and Research |
| spelling | doaj.art-1883aae79a8c4059bf35136750a50b772022-12-22T03:32:02ZengKorea Geriatrics SocietyAnnals of Geriatric Medicine and Research2508-47982017-09-0121313113710.4235/agmr.2017.21.3.131agmr.2017.21.3.131Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase PathwaySung Hoon Yu0Hyung Joon Yoo1Dong Hyun Kang2Shin Je Moon3Jae Myung Yu4Division of Endocrinology and Metabolism, Hanyang University College of Medicine, Seoul, KoreaDivision of Endocrinology and Metabolism, Hallym University College of Medicine, Seoul, KoreaDivision of Endocrinology and Metabolism, Hallym University College of Medicine, Seoul, KoreaDivision of Endocrinology and Metabolism, Hallym University College of Medicine, Seoul, KoreaDivision of Endocrinology and Metabolism, Hallym University College of Medicine, Seoul, KoreaBackground : The acute glucose fluctuations in diabetes can be a risk factor of cardiovascular events. Nonetheless, the mechanism of action of intermittent hyperglycemia on the proliferation of vascular smooth muscle cells (VSMCs) is poorly understood. We compared the effects of exposure to constant and intermittent hyperglycemia on in vitro proliferation of aortic VSMCs from obese diabetic rats. Methods : VSMCs from Otsuka Long-Evans Tokushima Fatty (OLETF) rats were incubated for 72 hours with different glucose concentrations: a constant normal-glucose medium (4.8 mM), constant high-glucose medium (24.5 mM), normal- and high-glucose media alternating every 12 hours, and mannose (12.0 mM; an osmotic control for high glucose levels). The proliferation of VSMCs was analyzed by a 3-[4,5-dimethylthiazol-2-yl]-diphenyltetrazolium bromide (MTT) assay. The molecular mechanism (including phospho-p44/42 mitogen-activated protein kinase [MAPK], mitogen-activated protein kinase kinase-1/2 (MEK1/2), Protein kinase B (Akt), and the apoptosis pathway) was then studied. Results : We detected enhanced proliferation of VSMCs incubated with the constant or intermittent high-glucose medium using the MTT assay (p<0.05). The proliferation of VSMCs was more pronounced in the intermittent high-glucose environment than at a constant high glucose concentration. In western blot analysis, treatment with the constant high-glucose medium for 72 hours increased phospho-p44/42 MAPK and phospho-MEK1/2 expression as compared to treatment with the normal-glucose medium. These effects were further enhanced by the intermittent high glucose concentration. Akt and phospho-Akt were not affected by hypergly cemia. In the apoptotic pathway, Bcl-xL, phospho-Bad, and caspase-3 were not affected by hyperglycemia for 72 hours. Conclusion : Hyperglycemia increased the proliferation of VSMCs from OLETF rats via the MAPK pathway. These effects were further enhanced by intermittent exposure to the high glucose concentration.http://www.e-agmr.org/journal/view.html?doi=10.4235/agmr.2017.21.3.131Intermittent high glucoseVascular smooth muscle cellMitogen-activated protein kinaseApoptosis |
| spellingShingle | Sung Hoon Yu Hyung Joon Yoo Dong Hyun Kang Shin Je Moon Jae Myung Yu Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway Annals of Geriatric Medicine and Research Intermittent high glucose Vascular smooth muscle cell Mitogen-activated protein kinase Apoptosis |
| title | Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway |
| title_full | Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway |
| title_fullStr | Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway |
| title_full_unstemmed | Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway |
| title_short | Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway |
| title_sort | intermittent high glucose enhances the proliferation of rat aortic vascular smooth muscle cells more than constant high glucose via the mitogen activated protein kinase pathway |
| topic | Intermittent high glucose Vascular smooth muscle cell Mitogen-activated protein kinase Apoptosis |
| url | http://www.e-agmr.org/journal/view.html?doi=10.4235/agmr.2017.21.3.131 |
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