ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Mengdi Wang,Zhuoran Zhang,Qingqing Huo,Maolong Wang,Yong Sun,Hongling Liu,Jing Chang,Bin He,Yan Liang
Mangiferin (MGF) is found in many natural plants, such as Rhizoma Anemarrhenae, and has anti-diabetes effects. However, its clinical applications and development are limited by poor solubility and low-concentration enrichment in pancreatic islets. In this paper, targeted polymeric nanoparticles were constructed for MGF delivery with the desired drug loading content (6.86 ± 0.60%), excellent blood circulation, and missile-like delivery to the pancreas. Briefly, Glucagon-like peptide 1 (GLP-1) as an active targeting agent to the pancreas was immobilized on the block copolymer polyethyleneglycol-polycaprolactone (PEG-PCL) to obtain final GLP-1-PEG-PCL amphiphiles. Spherical MGF-loaded polymeric nanoparticles were acquired from the self-assembly of the targeted GDPP nanoparticles and MGF with a homogeneous size of 158.9 ± 1.7 nm and a negative potential for a good steady state in circulation. In this drug vehicle, GLP-1 acts as the missile vanguard via the GLP-1 receptor on the surface of the pancreas for improving the accumulation and efficiency of MGF in the pancreas, the hypoglycemic effect of MGF, and the restorative effect on pancreatic islets, which were investigated. As compared to free MGF, MGF/GDPP nanoparticles appeared to be more concentrated in the pancreas, with better blood glucose and glucose tolerance, enhanced insulin levels, increased β-cell proliferation, reduced β-cell apoptosis, and islet repair in vivo. This targeted drug delivery system provided a novel strategy and hope for enhancing MGF delivery and anti-diabetes efficacy.
研究领域:
药学
·
纳米技术
·
糖尿病研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL RESEARCH
·
2020
·Vol. 53
·期 1
·1-12
·
IF 3.092
Tian Xusheng,Zhang Yukun,Li Han,Li Yunfeng,Wang Ning,Zhang Wei,Ma Boyan
Background The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance.Methods Male Sprague–Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells.Results Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased β cell mass after the treatment of PAL. We further found out that PAL could alleviate the β cell apoptosis that accounts for β cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress β cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the β cell apoptosis and JNK signaling in vitro.Conclusion In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.
研究领域:
药理学
·
内分泌学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUCLEAR MEDICINE AND BIOLOGY
·
2024
·
IF 3.6
Yuli Sun,Guangwen Li,Haiyan Hong,Lin Zhu,Hank F. Kung,Yan Zhang,Jinxia Zhu
Objective Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo , which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [ 125 I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). Methods In vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. Results In vitro cell studies showed that the concentration of [ 125 I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [ 125 I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. Conclusions The SERT imaging agent, [ 125 I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.
研究领域:
医学影像学
·
内分泌学
·
糖尿病研究
✓ 已验证
DOI
高影响因子
Environmental Science-Processes & Impacts
·
2025
·
IF 3.9
Xiaomin Ren,Jianying Wang,Fenqing Zhao,Pingping Zhang,Huan He,Zhixiang Xu,Bin Huang,Xuejun Pan
Previous studies have indicated that 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFAES), a substitute for perfluorooctane sulfonate (PFOS), caused disruptions in glucose metabolism, but its toxicological mechanisms remain unclear. Pancreatic β cells are responsible for regulating glucose metabolism. This study used mouse insulinoma β cells (β-TC-6) to study the toxic effects of 6:2 Cl-PFAES and elucidate its potential mechanisms. Through cell counting kit-8, trypan blue staining, and apoptosis assays, we found that 6:2 Cl-PFAES showed toxicity to β-TC-6 cells, even surpassing that of PFOS. Mechanistic studies demonstrated that 6:2 Cl-PFAES induced oxidative stress by ascendant levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside increased superoxide dismutase (SOD) activity. The oxidative stress-inducing capability of 6:2 Cl-PFAES was stronger than PFOS. Co-exposure with N-acetyl-L-cysteine (NAC), as the ROS scavenger, which obviously reduced the degree of cell apoptosis and the production of ROS, highlighting oxidative stress as a crucial mechanism of 6:2 Cl-PFAES-induced cell death. Transcriptomic analysis further revealed that 6:2 Cl-PFAES affected genes association with the oxidative phosphorylation pathway, confirming the oxidative stress effect, and altered diabetes-related genes expression, suggesting a heightened risk of diabetes. This study provides insights into the toxicity of 6:2 Cl-PFAES on β cells and its potential risks on glucose metabolism disruption.
研究领域:
毒理学
·
分子生物学
·
环境健康科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2021
·Vol. 179
·期 9
·1962-1977
·
IF 8.74
Jianxin Jia,Qi Kang,Shunzhi Liu,Yabin Song,Florence Susan Wong,Yingkun Qiu,Mingyu Li
Background and Purpose Recently, the antimalarial drug, artemether and the neurotransmitter GABA were identified to convert alpha cells into beta-like cells in vivo . However, some of these observations were challenged by other studies. To help address the controversy, we took advantage of zebrafish as a model to perform this study. Experimental Approach First, we performed a small-molecule screening for artemether and its skeleton analogues. Second, we used the Cre-LoxP system for lineage tracing to indicate the conversion of alpha cells into beta cells in vivo . The stable transgenic ins2:eGFP αTC1-6-cell line was used for evaluation of alpha-cell transdifferentiation in vitro . We further used multiple zebrafish transgenic and mutation lines to demonstrate beta-cell differentiation, beta-cell ablation and alpha-cell hyperplasia in this study. Key Results We showed that artemether and another sesquiterpene, aspterric acid, induced alpha-cell transdifferentiation into beta cells, both in zebrafish as well as using αTC1-6 cells. Furthermore, these two compounds also converted alpha cells into beta cells when beta cells were lost or alpha cells were hyperplastic in zebrafish. Unlike the previous report, the conversion of alpha cells to beta cells was mediated by increasing Pax4 expression, but not suppression of Arx expression. Conclusion and Implications Our data suggest that in zebrafish and αTC1-6 cells, both artemether and aspterric acid induce alpha-cell transdifferentiation. Our data, along with those of Li et al. (2017), suggested that artemether and aspterric acid were able to induce alpha-cell transdifferentiation, at least in zebrafish and αTC1-6 cells. Graphical Artemether and aspterric acid induced alpha-cell to beta-cell conversion but did not induced progenitor cell differentiation or exiting beta replication. The conversion of alpha cells to beta cells was mediated by increasing Pax4 expression.
研究领域:
药理学
·
发育生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Xiang Zhao,Wei Xue,Weixiao Ding,Yalei Qiao,Xuehui Chu,Yudong Qiu,Min Tang,Dongping Sun,Xiao Fu
Type 1 diabetes mellitus (T1DM) are characterized by blood glucose elevation with pancreatic β cells deficiency. As a safe alternative to frequent subcutaneous insulin injection, pancreatic β cell transplantation provides a promising therapeutic option for blood glucose control in T1DM. However, pancreatic β cell transplantation faces intractable challenges of the poor viability and severe host immune rejection. Therefore, a novel approach capable of improving the poor oxygen/nutrients supply and severe host immune rejection is highly desired. Herein, a novel biohybrid artificial pancreas, presenting glucose-dependent insulin release behavior, is constructed via pancreatic β cells encapsulating in a hydrogel scaffold. The hydrogel scaffold is made of the commixture of sodium alginate (SA), chitosan (CS) and sulfated bacterial cellulose (SBC). The biocompatible three-dimensional (3D) hydrogels protected pancreatic β cells from immune response but also allowed the exchange of nutrients and insulin. As a result of the synergistic effect, the biohybrid artificial pancreas can reverse the hyperglycemia and achieve sustained glycemic control for at least 30 days in diabetic mice. Collectively, we consider that this biohybrid artificial pancreas with an elaborate structure could provide an effective option for the treatment of type 1 diabetes.
研究领域:
生物医学工程
·
糖尿病治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2019
·Vol. 2
·期 5
·1800136
·
IF 0
Yalu Zou,Yuanyuan Wang,Shengsheng Zhang,Yuntang Wu,Xiaofei Liu
Islet β cell failure is a critical metabolic disorder in the development of type 2 diabetes (T2DM), and the decreased viability and dysfunction of β cells accelerate diabetic pathogenesis in association with higher mortality. In this study, the therapeutic effects of chitooligosaccharide biguanide (COSG), which is similar in structure to metformin and has negligible side effects, on islet β-cell dysfunction and the possible mechanism are explored. Streptozocin-induced diabetic rats are administered COSG via daily intragastric gavage for 8 weeks. COSG significantly controlled body weight loss, attenuated glucose levels in blood and urine, and increased serum insulin. Histological examination of the pancreas reveals that COSG also alleviated pancreatic atrophy in T2DM rats. Furthermore, COSG stimulated insulin receptor substrate-2 (IRS-2) signaling in rat islet β cells, thereby mediating the activation of the phosphatidylinositol 3 kinase/protein kinase (PI3K/Akt) signaling pathway. In addition, COSG promoted downstream forkhead transcription factor O1 (FoxO1) nuclear output to potentially activate pancreas duodenum homeobox-1 (PDX-1)/glucose transporter type-2 (GLUT-2)/glucose kinase (GCK) pathway-regulated insulin secretion. COSG also inhibited the glycogen synthase kinase-3β (GSK-3β)/caspase-3 pathway to prevent cell apoptosis. The intrinsic protective effects of COSG on the impaired insulin signaling system to delay β-cell apoptosis, increase β-cell growth and proliferation, improve β-cell function and promote insulin secretion highlight the possibilities of COSG as a novel strategy for the prevention of T2DM.
研究领域:
医学
·
内分泌学
✓ 已验证
产品关联
DOI
RSC Advances
·
2016
·Vol. 6
·期 107
·105690-105698
·
IF 3.289
Qing Sun,Juan Zhao,Yuan Zhang,Hongjie Yang,Ping Zhou
The self-association of human islet amyloid polypeptide (IAPP) into cytotoxic fibrillar assemblies that induce pancreatic β-cell apoptosis has been postulated as one of the major contributors to the development of type 2 diabetes (T2D). Hence, preventing IAPP amyloid fibrillation and β-cell apoptosis is regarded as a promising treatment for T2D. Intrigued by our previous findings that a natural amphiphilic hyperbranched proteoglycan from Ganoderma lucidum, named FYGL, can decrease plasma glucose level in vivo, we demonstrated here that FYGL efficiently inhibits IAPP fibrillation and attenuates β-cell apoptosis, using a combination of biophysical, calculation and cell culture methods, including thioflavin T (ThT) and 8-anilino-1-naphthalene sulfonate (ANS) fluorescence spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM), circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), nuclear magnetic resonance (NMR) spectroscopy, molecular docking, cell viability tests and laser scanning confocal microscopy imaging. Moreover, a universally applicable inhibition mechanism proposed that FYGL blocks the interpeptide interaction and stabilizes IAPP structure in an α-helical conformation by forming multiple hydrogen bonds with IAPP. The findings of this study warrant FYGL to be further investigated as a potential therapeutic treatment and may provide a valuable reference for medicinal chemistry in the development of drugs against T2D as well as other amyloid diseases such as Alzheimer's disease and Huntington's disease.
研究领域:
生物化学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Jie Liu,Mei-qi He,Gao-peng Guan,Xin-xing Wan,Ping Jin
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms. Despite a significant increase in ISG15 levels following viral infection, the specific role of ISG15 in the impairment of insulin-producing β-cells is unclear. To address this issue at the clinical level, we conducted this experimental work, and found elevated levels of ISG15 in the peripheral blood of T1D patients, suggesting a potential link between ISG15 and T1D. In the T1D animal model, we discovered that both ISG15 levels and cellular apoptosis were increased in pancreatic islet tissue. To investigate at the cellular level, we cultured MIN6 cells in the presence of supernatants derived from iBMDM cells transfected with poly(I:C) (PIC), a viral mimic. This exposure led to an upregulation of ISG15 expression in MIN6 cells, which was accompanied by the suppression of their functional capabilities and viability. Intriguingly, the direct transfection of MIN6 cells with PIC increased the expression of ISG15. We further found that elevated levels of ISG15 had a direct inhibitory effect on insulin secretion and it also contributed to β-cell apoptosis in a TNF-α-dependent manner. In conclusion, our study revealed a potential underlying mechanism through which ISG15 increases the apoptosis of β-cells, providing valuable insights that could facilitate the development of T1D treatment strategies.
研究领域:
免疫学
·
内分泌学
·
糖尿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2022
·Vol. 2022
·期 1
·5648896
·
IF 3.246
Xue-Qin Li,Shan-Shan Jia,Ke Yuan,Song-Heng Jin
Content . The water and ethanol extracts of Torreya grandis ( T. grandis ) have antioxidant, antibacterial, and hypolipidemic effects . Objective . The hypoglycemic effect and mechanism of the n-butanol fraction of the 75% ethanol extract of T. grandis leaves (BFTL) on rats with streptozotocin- and high-fat diet-induced type 2 diabetes mellitus (T2DM) were investigated. Materials and Methods . Sprague–Dawley rats were randomly divided into six groups: control, T2DM, metformin, high-dose BFTL (800 mg/kg), middle-dose BFTL (400 mg/kg), and low-dose BFTL (200 mg/kg). After 4 weeks of BFTL treatment, the correlations of serum indicators with protein expression in tissue were determined, and pathological changes in the liver, kidneys, and pancreas were analyzed. Results . Compared with the results in the T2DM group, serum fasting blood glucose, triglyceride, total cholesterol, malondialdehyde, alanine aminotransferase, and aspartate aminotransferase levels were significantly decreased ( p < 0.05), whereas superoxide dismutase and glutathione peroxidase levels were significantly increased ( p < 0.05) in the high-, middle-, and low-dose BFTL groups. The treatment also improved oral glucose tolerance. In addition, the pathological changes of the liver, kidney, and pancreas were improved by BFTL treatment. Cytochrome and caspase-3 expression in pancreatic was significantly decreased ( p < 0.05) by BFTL treatment, whereas the Bcl-2/Bax ratio was significantly increased ( p < 0.05). Discussion and Conclusion . BFTL exerted significant hypoglycemic effect on T2DM model rats, and its mechanism involved the suppression of blood glucose levels and oxidative stress by improving the metabolism of blood lipids and antioxidant capacity, boosting β -cell function, and inhibiting β -cell apoptosis.
研究领域:
药理学
·
糖尿病学
·
分子生物学
✓ 已验证
DOI
高影响因子
Genes & Genomics
·
2022
·Vol. 44
·期 7
·867-878
·
IF 2.164
Li Mo,She Jiang,Ma Louyan,Ma Li,Ma Xiaorui,Zhai Jiajia
Background Destruction of pancreatic beta cells is the most typical characteristic of diabetes. Objective We aimed to evaluate the effect of berberine (BBR), a bioactive isoquinoline derivative alkaloid, on beta cell injury. Methods Rodent pancreatic beta cell line INS-1 was treated with 0.5 mM palmitate (PA) for 24 h to establish an in vitro beta cell injury model. Results BBR at 5 µM promoted cell viability, inhibited cell apoptosis and enhanced insulin secretion in PA-induced INS-1 cells. BBR treatment also suppressed PA-induced oxidative stress in INS-1 cells, as evidenced by the decreased ROS production and increased activities of antioxidant enzymes. In addition, suppressed ATP production and reduced mitochondrial membrane potential were restored by BBR in PA-treated INS-1 cells. It was further determined that BBR affected the expressions of mitophagy-associated proteins, suggesting that BBR promoted mitophagy in PA-exposed INS-1 cells. Meanwhile, we found that BBR facilitated nuclear expression and DNA-binding activity of Nrf2, an antioxidative protein that can regulate mitophagy. Finally, a rescue experiment was performed and the results demonstrated that the effect of BBR on cell viability, apoptosis and mitochondrial function in PA-induced INS-1 cells were cancelled by PINK1 knockdown. Conclusions BBR protects islet β cells from PA-induced injury, and this protective effect may be achieved by regulating mitophagy. The present study may provide a novel therapeutic strategy for β cell injury in diabetes mellitus.
研究领域:
药理学
·
细胞生物学
·
糖尿病
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Qingli Qu,Xiaoli Zhang,Hossein Ravanbakhsh,Guosheng Tang,Jian Zhang,Yankang Deng,Kevin Braeckmans,Stefaan C. De Smedt,Ranhua Xiong,Chaobo Huang
Core-shell multicompartmental microparticles have gained increasing attention as their architecture resembles the multicompartmental composition of eukaryotic cells. However, challenges remain in the fabrication of biocompatible multicompartmental microparticles at a sufficiently high scale. Herein, all-aqueous ‘mangosteen-like’ core–shell multicompartmental microparticles were created by an oil-free gas-shearing fabrication approach. Both the shell thickness and core size of thus obtained mangosteen-like microparticles can be easily finetuned. Mangosteen-like particles have well segregated (up to eight) compartments which are attractive to precisely control enzymatic cascade reactions. To illustrate the application potential, insulin releasing mangosteen-like microparticles (‘artificial pancreatic beta cells’) were developed.
研究领域:
生物工程
·
材料科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）