Diabetes & Metabolism Journal

Original Articles

An In Vitro Model to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia: Kusampudi Shilpa, Thangaraj Dinesh, Baddireddi Subhadra Lakshmi; Diabetes Metab J. 2013;37(3):176-180. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.176

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Background

The aim of this study was an in vitro investigation of the effect of high glucose concentration on adipogenesis, as prolonged hyperglycemia alters adipocyte differentiation.

Methods

3T3-L1 preadipocytes differentiated in the presence of varying concentrations of glucose (25, 45, 65, 85, and 105 mM) were assessed for adipogenesis using AdipoRed (Lonza) assay. Cell viability and proliferation were measured using MTT reduction and [³H] thymidine incorporation assay. The extent of glucose uptake and glycogen synthesis were measured using radiolabelled 2-deoxy-D-[1-³H] glucose and [¹⁴C]-UDP-glucose. The gene level expression was evaluated using reverse transcription-polymerase chain reaction and protein expression was studied using Western blot analysis.

Results

Glucose at 105 mM concentration was observed to inhibit adipogenesis through inhibition of CCAAT-enhancer-binding proteins, sterol regulatory element-binding protein, peroxisome proliferator-activated receptor and adiponectin. High concentration of glucose induced stress by increasing levels of toll-like receptor 4, nuclear factor κB and tumor necrosis factor α thereby generating activated preadipocytes. These cells entered the state of hyperplasia through inhibition of p27 and proliferation was found to increase through activation of protein kinase B via phosphoinositide 3 kinase dependent pathway. This condition inhibited insulin signaling through decrease in insulin receptor β. Although the glucose transporter 4 (GLUT4) protein remained unaltered with the glycogen synthesis inhibited, the cells were found to exhibit an increase in glucose uptake via GLUT1.

Conclusion

Adipogenesis in the presence of 105 mM glucose leads to an uncontrolled proliferation of activated preadipocytes providing an insight towards understanding obesity.

Citations

Citations to this article as recorded by

Adipogenesis-Related Metabolic Condition Affects Shear-Stressed Endothelial Cells Activity Responding to Titanium
Thaís Silva Pinto, Anderson Moreira Gomes, Paula Bertin de Morais, Willian F. Zambuzzi
Journal of Functional Biomaterials.2023; 14(3): 162. CrossRef
Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes
Adam Wróblewski, Justyna Strycharz, Ewa Świderska, Aneta Balcerczyk, Janusz Szemraj, Józef Drzewoski, Agnieszka Śliwińska
International Journal of Molecular Sciences.2021; 22(13): 6964. CrossRef
Effects of high glucose conditions on the expansion and differentiation capabilities of mesenchymal stromal cells derived from rat endosteal niche
Ahmed Makki A. Al-Qarakhli, Norhayati Yusop, Rachel J. Waddington, Ryan Moseley
BMC Molecular and Cell Biology.2019;[Epub] CrossRef
Inhibition of WNT/β-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells
Hiroshi Harada, Yojiro Tsuda, Kei Yabuki, Eisuke Shiba, Kazuyoshi Uchihashi, Atsuji Matsuyama, Yoshihisa Fujino, Toru Hachisuga, Masanori Hisaoka
Laboratory Investigation.2018; 98(4): 439. CrossRef
Effects of high glucose on caveolin-1 and insulin signaling in 3T3-L1 adipocytes
Sara Palacios-Ortega, Maider Varela-Guruceaga, J. Alfredo Martínez, Carlos de Miguel, Fermín I. Milagro
Adipocyte.2016; 5(1): 65. CrossRef
Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications
Meghan A Piccinin, Zia A Khan
Adipocyte.2014; 3(4): 263. CrossRef
Letter: AnIn VitroModel to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia (Diabetes Metab J2013;37:176-80)
In-Kyung Jeong
Diabetes & Metabolism Journal.2013; 37(4): 296. CrossRef
Response: AnIn VitroModel to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia (Diabetes Metab J2013;37:176-80)
Kusampudi Shilpa, Thangaraj Dinesh, Baddireddi Subhadra Lakshmi
Diabetes & Metabolism Journal.2013; 37(4): 298. CrossRef

The Effect of alpha-Lipoic Acid on Vascular Smooth Muscle Cell Proliferation, Migration, Neointimal Formation and PAI-1 Expression.: Dong Woo Shin, Dong Wook Lee, Sang Jun Lee, Hye Soon Kim, Hyo Gyoung Kang, Jong Deok Ahn, In Kyu Lee; Korean Diabetes J. 2001;25(6):446-459. Published online December 1, 2001

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Abstract PDF: BACKGROUND
Exposure to large amounts of glucose causes a characteristic dysfunction and morphologic changes of the endothelium by an increased production of reactive oxygen species (ROS) in diabetes. The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in vascular smooth muscle cells (VSMC). Antioxidants have been proposed to inhibit multiple proatherogenic events. This study investigated the effect of (alpha)-Lipoic acid on PAI-1 expression and VSMC proliferation and migration both in vivo and in vitro. METHODS: In the in vitro study, cultured rat aortic smooth muscle cells (RASMC) were incubated in a medium containing high glucose (22 mM) and 100 nM angiotensin II for 4 hour. After (alpha)-Lipoic acidtreatment, a -migration and growth assay of the RASMC, and a gel mobility shift assay and reporter gene analysis for nuclear factor- B (NF-kappa B) and northern blot analysis for PAI-1 were performed. In the in vivo study, the effect of (alpha)-Lipoic acid on neointimal hyperplasia in a rat carotid balloon injury model was evaluated. RESULTS: RASMC migration was inhibited significantly by (alpha)-Lipoic acid (p<0.01), but their proliferation was not inhibited. The NF-kappa B DNA binding activity and NF-kappa B promoter activity was inhibited by (alpha)-Lipoic acid significantly (p<0.01). (alpha)-Lipoic acid inhibited PAI-1 mRNA expression by high glucose and angiotensin II in dose dependent manner (p<0.05). In the rat carotid artery balloon injury model, neointimal formation was reduced by (alpha)-Lipoic acid treatment in a dose dependent manner significantly (p<0.01). CONCLUSION: (alpha)-Lipoic acid suppresses migration, but not proliferation in RASMC. (alpha)-Lipoic acid also reduce neointima formation in a rat carotid balloon injured model. This effect might be related to the blocking of NF-kappa B which increase the expression of the genes associated with atherosclerosis including TNF-alpha, IL-1, IL-6, endothelin-1, MCP-1, VCAM-1, ICAM-1, E-selectin, tissue factor.

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