Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway

Cui, Jia; Duan, Jialin; Chu, Jianjie; Guo, Chao; Xi, Miaomiao; Li, Yang; Weng, Yan; W, Guo; Yin, Ying; Wen, Aidong; Qiao, Boling

doi:10.18632/aging.102702

Cited by 13 publications

(11 citation statements)

References 52 publications

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“…CHS, one triterpenoid saponin with many pharmacological activities, is abundantly found in various medicinal plants, such as Panax japonicus , Aralia taibaiensis , and other plants. In previous studies, we had shown its protective effects against oxidative damage in cardiomyocytes and brain cells, and beneficial effects on intermittent hyperglycemia induced pancreatic islet injuries [ 24 , 31 , 32 ]. However, its effects against lipotoxicity-induced pancreatic islet injuries were largely unknown to us.…”

Section: Discussionmentioning

confidence: 99%

IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity

Wang

Duan

Jia

et al. 2021

Oxidative Medicine and Cellular Longevity

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Chronic hyperlipidemia leads to pancreatic β-cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; however, its protective effects against lipotoxicity-induced β-cell oxidative stress and dysfunction are not clear. This study was designed to investigate the effects of CHS against lipotoxicity-induced β-cell injuries and its possible mechanism involved. High-fat (HF) diet and a low dose of streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) model in vivo and βTC3 cells subjected to 0.5 mM palmitate (PA) to imitate the lipotoxic model in vitro were performed. Pancreatic functions, ROS, and antioxidant protein measurements were performed to evaluate the effects of CHS on cell injuries. Protein expression levels were measured by Western blotting. Furthermore, siRNA-targeted Nrf2, PI3K/Akt inhibitor (LY294002), or GSK-3β inhibitor (LiCl) was used to investigate the crosstalk relationships between proteins. As the results showed, CHS treatment inhibited apoptosis, promoted insulin release, and reduced oxidative stress. CHS treatment significantly increased the expression of Nrf2 in the cytoplasm and nuclear protein. The antioxidative and benefit effects of CHS were inhibited by siNrf2. The phosphorylation of IRS-2, PI3K, Akt, and GSK-3β was markedly increased by CHS which were inhibited by PA. In addition, inhibition of PI3K/Akt or GSK-3β with specific inhibitors dramatically abrogated the protective effects of CHS, revealing that the IRS-2/Akt/GSK-3β signaling axis was involved in the protective effects of CHS. These results demonstrate that CHS protected βTC3 cells against PA-induced oxidative stress and cell dysfunction through Nrf2 by the IRS-2/Akt/GSK-3β-mediated pathway.

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Section: Discussionmentioning

confidence: 99%

IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity

Wang

Duan

Jia

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Several WNT pathways, such as WNT3a/β‐catenin 204–206 and WNT4/PCP, 207 could improve β cell proliferation and insulin secretion. In‐depth dissections revealed that the activation of TCF7L2 and FoxO1 is key to this proproliferation effect of WNT3a/β‐catenin pathway 187,208,209 . TCF7L2 is crucial to maintaining the normal functions of β cells, and its silencing can inhibit GSIS through regulating the expression of genes that control the fusion of secretory granule, such as syntaxin 1A, and syntaxin‐binding protein 1 210 .…”

Section: Signaling Pathways In T2dmmentioning

confidence: 99%

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

Cao

Tian

Zhang

et al. 2023

MedComm

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Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID‐19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.

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“…The knockout of Wnt10b in vivo leads to an increased potential for the trans-differentiation of myoblasts into adipocytes and the acquisition of adipocyte characteristics during muscle regeneration ( Taylor-Jones et al, 2002 ; Vertino et al, 2005 ). Components of the Wnt pathway are abundantly expressed in the pancreas and tissues of the small intestine, thereby playing a role in the direct or indirect regulation of the functionality of pancreatic β-cells ( Cui et al, 2020 ). In vitro studies have shown that Wnt signaling molecules regulate a variety of cell cycle regulators and then promote the growth and proliferation of islet β-cells ( Rulifson et al, 2007 ; Yoshihara et al, 2020 ).…”

Section: The Wnt Signaling Pathway and Diabetesmentioning

confidence: 99%

The Wnt Signaling Pathway in Diabetic Nephropathy

Wang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Diabetic nephropathy (DN) is a serious kidney-related complication of both type 1 and type 2 diabetes mellitus (T1DM, T2DM) and the second major cause of end-stage kidney disease. DN can lead to hypertension, edema, and proteinuria. In some cases, DN can even progress to kidney failure, a life-threatening condition. The precise etiology and pathogenesis of DN remain unknown, although multiple factors are believed to be involved. The main pathological manifestations of DN include mesangial expansion, thickening of the glomerular basement membrane, and podocyte injury. Eventually, these pathological manifestations will lead to glomerulosclerosis, thus affecting renal function. There is an urgent need to develop new strategies for the prevention and treatment of DN. Existing evidence shows that the Wnt signaling cascade plays a key role in regulating the development of DN. Previous studies focused on the role of the Wnt canonical signaling pathway in DN. Subsequently, accumulated evidence on the mechanism of the Wnt non-canonical signaling indicated that Wnt/Ca2+ and Wnt/PCP also have essential roles in the progression of DN. In this review, we summarize the specific mechanisms of Wnt signaling in the occurrence and development of DN in podocyte injury, mesangial cell injury, and renal fibrosis. Also, to elucidate the significance of the Wnt canonical pathway in the process of DN, we uncovered evidence supporting that both Wnt/PCP and Wnt/Ca2+ signaling are critical for DN development.

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Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway

Cited by 13 publications

References 52 publications

IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity

IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

The Wnt Signaling Pathway in Diabetic Nephropathy

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