Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J mouse

Zhu, Jian; Su, Liping; Ye, Lei; Lee, Kok-Onn; Ma, Jianhua

doi:10.1016/j.diabres.2011.12.009

Cited by 14 publications

(14 citation statements)

References 30 publications

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“…Diabetic KK-Ay mice have been frequently used as an animal model for non-insulin-dependent diabetes [17], [18]. The symptoms of this animal model are similar to those of diabetic patients.…”

Section: Methodsmentioning

confidence: 99%

Promoting Effects of the Adipokine, Apelin, on Diabetic Nephropathy

Zhang

Wang

et al. 2013

PLoS ONE

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Angiogenesis, increased glomerular permeability, and albuminuria are thought to contribute to the progression of diabetic nephropathy (DN). Apelin receptor (APLNR) and the endogenous ligand of APLNR, apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of apelin in the pathogenesis of DN. Therefore, we observed apelin/APLNR expression in kidneys from patients with type 2 diabetes as well as the correlation between albuminuria and serum apelin in patients with type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of apelin on glomerular endothelial cells. To measure the permeability of apelin in glomerular endothelial cells, we used transwells to detect FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum apelin was significantly higher in the patients with type 2 diabetes compared to healthy people (p<0.05, Fig. 1B) and that urinary albumin was positively correlated with serum apelin (R = 0.78, p<0.05). Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05). Apelin also promoted the permeability of glomerular endothelial cells (p<0.05) and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05). These results indicated that upregulated apelin in type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.

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Section: Methodsmentioning

confidence: 99%

Promoting Effects of the Adipokine, Apelin, on Diabetic Nephropathy

Zhang

Wang

et al. 2013

PLoS ONE

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“…Tβ 4 was recently shown to attenuate hyperglycaemia and improve insulin resistance in diabetic mice (Zhu et al . ). However, the effect of Tβ 4 on RAGE, which is a critical cause of diabetic injury in patients, has not yet been investigated.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, it has been demonstrated that Tβ 4 is involved in the protection and recovery from diabetic injury and exerts its properties via anti-apoptotic, anti-inflammatory and angiogenic functions both in vitro and in vivo (Malinda et al 1999). Tβ 4 was recently shown to attenuate hyperglycaemia and improve insulin resistance in diabetic mice (Zhu et al 2012). However, the effect of Tβ 4 on RAGE, which is a critical cause of diabetic injury in patients, has not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

Actin cytoskeletal rearrangement and dysfunction due to activation of the receptor for advanced glycation end products is inhibited by thymosin beta 4

Kim

Kwon

2015

The Journal of Physiology

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Key pointsr Thymosin beta 4 (Tβ 4 ) attenuates the vascular cellular toxicity induced by advanced glycation end products (AGEs) in human umbilical vein endothelial cells (HUVECs).r Tβ 4 reduces expression of both the receptor of AGEs (RAGE) and the filamentous actin (F-actin) to globular actin (G-actin) ratio.r RAGE expression was regulated by actin cytoskeleton involved in Tβ 4 . r Tβ 4 attenuates the vascular cellular toxicity induced by AGEs via remodelling of the actin cytoskeleton.r AGEs attenuate vascular-like tube formation of HUVECs, which is reversed by Tβ 4 via remodelling of the actin cytoskeleton. AbstractThe receptor of advanced glycation end products (RAGE) is a cell-surface receptor that is a key factor in the pathogenesis of diabetic complications, including vascular disorders. Dysfunction of the actin cytoskeleton contributes to disruption of cell membrane repair in response to various type of endothelial cell damage. However, mechanism underlying RAGE remodelling of the actin cytoskeleton, by which globular actin (G-actin) forms to filamentous actin (F-actin), remains unclear. In this study we examined the role of thymosin beta 4 (Tβ 4 ) -which binds to actin, blocks actin polymerization, and maintains the dynamic equilibrium between G-actin and F-actin in human umbilical vein endothelial cells (HUVECs) -in the response to RAGE. Tβ 4 increased cell viability and decreased levels of reactive oxygen species in HUVECs incubated with AGEs. Tβ 4 reduced the expression of RAGE, consistent with a down-regulation of the F-actin to G-actin ratio. The effect of remodelling of the actin cytoskeleton on RAGE expression was clarified by adding Phalloidin, which stabilizes F-actin. Moreover, small interfering RNA was used to determine whether intrinsic Tβ 4 regulates RAGE expression in the actin cytoskeleton. The absence of intrinsic Tβ 4 in HUVECs evoked actin cytoskeleton disorder and increased RAGE expression. These findings suggest that regulation of the actin cytoskeleton by Tβ 4 plays a pivotal role in the RAGE response to AGEs. Abbreviations AGEs, advanced glycation end products; GSK, glycogen synthase kinase; HUVEC, human umbilical vein endothelial cell; RAGE, receptor of advanced glycation end products; ROS, reactive oxygen species; Tβ 4 , thymosin beta 4; VEGFR, vascular endothelial growth factor receptor.

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“…Tβ4 is angiogenic and can promote EC migration and adhesion, tubule formation, aortic ring sprouting, and angiogenesis [44,45] . Tβ4 ameliorates hyperglycemia and improves insulin resistance in mouse model of type 2 diabetes [46] . We showed that EPCs derived from Zucker diabetic fatty rat have reduced angiogenic potential.…”

Section: Strategies To Enhance Epc Potencymentioning

confidence: 99%

“…Besides statins, losartan, an angiotensin II receptor antagonist drug, commonly used in hypertension, significantly improved impaired EPC function in hypertensive patients [42] . Tβ4, an actin sequestering protein, is found to possess angiogenic activity [44,45] and antidiabetic property [46] . Tβ4 is angiogenic and can promote EC migration and adhesion, tubule formation, aortic ring sprouting, and angiogenesis [44,45] .…”

Section: Strategies To Enhance Epc Potencymentioning

confidence: 99%

Enhancing endothelial progenitor cell for clinical use

Poh

2015

WJSC

Self Cite

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Circulating endothelial progenitor cells (EPCs) have been demonstrated to correlate negatively with vascular endothelial dysfunction and cardiovascular risk factors. However, translation of basic research into the clinical practice has been limited by the lack of unambiguous and consistent definitions of EPCs and reduced EPC cell number and function in subjects requiring them for clinical use. This article critically reviews the definition of EPCs based on commonly used protocols, their value as a biomarker of cardiovascular risk factor in subjects with cardiovascular disease, and strategies to enhance EPCs for treatment of ischemic diseases.

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Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J mouse

Cited by 14 publications

References 30 publications

Promoting Effects of the Adipokine, Apelin, on Diabetic Nephropathy

Promoting Effects of the Adipokine, Apelin, on Diabetic Nephropathy

Actin cytoskeletal rearrangement and dysfunction due to activation of the receptor for advanced glycation end products is inhibited by thymosin beta 4

Enhancing endothelial progenitor cell for clinical use

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