Nutrients
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2020
·Vol. 12
·期 6
·1889
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IF 4.546
Nancy Saji,Nidhish Francis,Lachlan J. Schwarz,Christopher L. Blanchard,Abishek B. Santhakumar
Oxidative stress is known to modulate insulin secretion and initiate gene alterations resulting in impairment of β-cell function and type 2 diabetes mellitus (T2DM). Rice bran (RB) phenolic extracts contain bioactive properties that may target metabolic pathways associated with the pathogenesis of T2DM. This study aimed to examine the effect of stabilized RB phenolic extracts on the expression of genes associated with β-cell function such as glucose transporter 2 (Glut2), pancreatic and duodenal homeobox 1 (Pdx1), sirtuin 1 (Sirt1), mitochondrial transcription factor A (Tfam), and insulin 1 (Ins1) in addition to evaluating its impact on glucose-stimulated insulin secretion. It was observed that treatment with different concentrations of RB phenolic extracts (25-250 µg/mL) significantly increased the expression ofGlut2,Pdx1,Sirt1, Tfam,andIns1genes and glucose-stimulated insulin secretion under both normal and high glucose conditions. RB phenolic extracts favourably modulated the expression of genes involved in β-cell dysfunction and insulin secretion via several mechanisms such as synergistic action of polyphenols targeting signalling molecules, decreasing free radical damage by its antioxidant activity, and stimulation of effectors or survival factors of insulin secretion.Keywords:rice bran;phenolic extracts;β-cell function;gene expression;insulin secretion
研究领域:
营养学
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分子生物学
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内分泌学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2020
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IF 4.268
Chunjun Wang,Jihong Yao,Linjie Ju,Xiaohua Wen,Luan Shu
Background Diabetes is characterized by β-cell loss and dysfunction. A strategy for diabetes treatment is to promote new β-cell formation. Puerarin is an isoflavone from the root of Pueraria lobata (Willd.) Ohwi . Our previous study demonstrated puerarin could ameliorate hyperglycemia in diabetic mice. However, related mechanisms and potential roles of puerarin in β-cell neogenesis have not been elucidated. Purpose The present study aims to investigate whether anti-diabetic effect of puerarin is dependent on promoting β-cell neogenesis via GLP-1R signaling activation. Methods A high-fat diet (HFD) induced diabetic mouse model was applied to investigate effects of puerarin in vivo , exendin-4 (GLP-1R agonist) and metformin were used as positive controls. Moreover, related mechanisms and GLP-1R downstream signal transduction were explored in isolated cultured mouse pancreatic ductal cells. Results Puerarin improved glucose homeostasis in HFD diabetic mice significantly. Markers of new β-cell formation (insulin, PDX1 and Ngn3) were observed in pancreatic ducts of HFD mice treated by puerarin. Of note, efficacy of puerarin in vivo was suppressed by GLP-1R antagonist exendin9-39, but enhanced by exendin-4 respectively. In cultured mouse pancreatic ductal cells, puerarin induced expressions of insulin and PDX1, upregulated GLP-1R expression and activated β-catenin and STAT3 subsequently. Expressions of insulin and PDX1 in ductal cells could be blocked by exendin9-39, or β-catenin inhibitor ICG001, or JAK2 inhibitor AG490 . Conclusion These data clarified puerarin ameliorated hyperglycemia of HFD mice via a novel mechanism involved promoting β-cell neogenesis. Our finding highlights the potential value of puerarin developing as an anti-diabetic agent.
研究领域:
药理学
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内分泌学
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糖尿病研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
World Journal of Stem Cells
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2025
·Vol. 17
·期 7
·104607
·
IF 3.6
Kun Wang,Wei Lin,Jun-Yong Han,Jin-Yan Chen,Rong-Hua Liu,Zhen Yu,Jing-Jun Jin
BACKGROUND Type 1 diabetes (T1D) results from the autoimmune-mediated loss of pancreatic β-cells. Current insulin therapies offer symptomatic relief but fall short of providing a definitive cure. Islet cell transplantation, while promising, faces limitations related to donor scarcity, procedural complexities, and the necessity for long-term immunosuppression. Consequently, there is an urgent need for innovative strategies aimed at β-cell regeneration. Patient-derived induced pluripotent stem cells (iPSCs), obtained from peripheral blood mononuclear cells (PBMCs) of T1D patients, hold great potential as a source of cells for therapeutic purposes. Therefore, the differentiation of T1D-iPSCs into functional pancreatic β-cells is a critical step toward effective β-cell replacement therapy. AIM To assess the potential of patient-derived T1D-β-like cells (differentiated from T1D-iPSCs reprogrammed from T1D-PBMCs) for restoring β-cell function in T1D. METHODS T1D-iPSCs were reprogrammed from T1D-PBMCs using an episomal vector-based approach. Pluripotency was confirmed by flow cytometry (FCM), quantitative real-time polymerase chain reaction, genomic stability analysis, and teratoma formation assays. Differentiation into pancreatic β-cells was optimized using triiodothyronine (T3), vitamin C (Vc), and an adenovirus (M3C) encoding pancreatic duodenal homeobox-1, neurogenin 3 ( Ngn3 ), and MAF bZIP transcription factor A ( MafA ). Following characterization of β-cell features by immunofluorescence, quantitative real-time polymerase chain reaction, and flow cytometry, therapeutic efficacy was assessed through blood glucose monitoring after transplantation under the renal capsule of streptozotocin-induced diabetic mice. RESULTS T1D-iPSCs were successfully generated from T1D-PBMCs. These cells exhibited the hallmark characteristics of pluripotent stem cells, including appropriate morphology, differentiation potential, genomic integrity, and expression of pluripotency-associated genes. Differentiation yielded insulin-positive (insulin + ) pancreatic β-like cells that, at the mRNA level, expressed key β-cell markers such as pancreatic duodenal homeobox-1, Ngn3 , MafA , NeuroD , glucagon-like peptide-1 receptor, Nkx6.1 , glucose transporter 2, and Kir6.2 . Notably, the T3 + Vc group displayed the lowest Ngn3 expression (1.31 ± 0.38 vs 1.96 ± 0.25 vs 2.51 ± 0.24, P < 0.01), while the M3C + T3 + Vc group exhibited the highest MafA expression (0.49 ± 0.11 vs 0.32 ± 0.06 vs 0.29 ± 0.08, P < 0.05). Both in vitro and in vivo assessments confirmed the insulin secretion ability of the generated β-like cells; however, they did not demonstrate appropriate modulation of insulin release in response to variations in extracellular glucose concentrations. CONCLUSION T1D-iPSCs derived from T1D-PBMCs can be differentiated into insulin + β-like cells, albeit with functional immaturity. These cells represent a potential source of seed cells for β-cell replacement therapy in T1D.
研究领域:
干细胞生物学
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糖尿病研究
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再生医学
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细胞分化
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基因表达
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转化医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2023
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IF 5.8
Chaofeng Xing,Minyi Tang,Jianqin Yang,Shuai Wang,Qihua Xu,Wenbin Feng,Yunping Mu,Fanghong Li,Allan Zijian Zhao
Type 1 diabetes mellitus (T1DM) is characterized by life-threatening absolute insulin deficiency . Although ω-3 polyunsaturated fatty acids (PUFAs) displayed significant anti-hyperglycemic activity, the insulinotropic effects of their metabolites remain unknown. In this study, we took advantage of a transgenic model , mfat-1, that overexpresses an ω-3 desaturase and can convert ω-6 PUFAs to ω-3 PUFAs. Eicosapentaenoic acid (EPA) was sharply elevated in the pancreatic tissues of mfat-1 transgenic mice compared with wild-type (WT) mice. In contrast to the WT mice, the mfat-1 transgenics did not develop overt diabetes and still maintained normal blood glucose levels and insulin secretion following streptozotocin-treatment. Furthermore, under the condition of pancreatic β-cell damage, co-incubation of the metabolites of EPA produced from the CYP 450 pathway with isolated islets promoted the overexpression of insulin as well as β-cell specific markers, pdx1 and Nkx6.1 in pancreatic α-cells. Addition of EPA metabolites to the cultured glucagon-positive α-cell lines, a series of pancreatic β-cell markers were also found significantly elevated. Combined together, these results demonstrated the effects of ω-3 PUFAs and their metabolites on the trans-differentiation from α-cells to β-cells and its potential usage in the intervention of T1DM.
研究领域:
内分泌学
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糖尿病研究
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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