FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Ting Xia,Chang-Shun Liu,Yan-Nan Hu,Zhen-Ye Luo,Fei-Long Chen,Li-Xia Yuan,Xiao-Mei Tan
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman’s analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC–MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.
研究领域:
药理学
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内分泌学
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微生物学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Baiyi Yan,Yanchun Gong,Wei Meng,Huizhen Sun,Wenxi Li,Kaizhi Ding,Caixia Dang,Xiaofei Gao,Wei Sun,Chunhua Yuan,Songhua Wang,Li-Hua Yao
Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C 10 H 13 N 5 O 3 ), a natural adenosine isolated from Cordyceps militaris , on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca 2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.
研究领域:
内分泌学
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代谢学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Zhang Yue,Wang Xiang,Deng Duping,Gong Yuanyuan,Chen Xuanyi,Li Juan,Hong Xiaojuan
Objective: This study aimed to investigate the impact of electroacupuncture (EA) on blood glucose levels, gut microbiota, short-chain fatty acids (SCFAs), and glucagon-like peptide-1 (GLP-1) in a rat model of type 2 diabetes mellitus (T2DM).Methods: Forty Sprague–Dawley (SD) rats were randomly assigned to five groups (n = 8/group) using a random number table: normal control, T2DM model, electroacupuncture (EA), EA + antibiotics (EA + A), and antibiotics (A). The normal rats received a standard diet and saline gavage, while the other groups were fed a high-fat diet and emulsion. The EA + A and A groups received additional antibiotic solution gavage. The normal, model, and A groups were immobilized and restrained for 30 min, six times per week, for 4 weeks. The EA and EA + A groups received EA treatment at specific acupoints for 30 min, six times per week, for 4 weeks. EA parameters were continuous waves at 10 Hz and 1–2 mA. During the intervention, water and food consumption, body weight, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) were monitored. Pancreatic tissue was examined using hematoxylin and eosin (H&E) staining. Fecal microbial communities were analyzed by 16S rDNA sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography–mass spectrometry (GC–MS). Serum levels of fasting insulin (FINS), glycated hemoglobin (HbA1c), and glucagon-like peptide-1 (GLP-1) were determined using enzyme-linked immunosorbent assay (ELISA).Results: EA significantly improved daily water intake, food consumption, and body weight in T2DM rats (p < 0.01). EA also reduced FBG, the area under the curve of the OGTT, FINS, and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM rats (p < 0.05). The ELISA results showed a lower concentration of HbA1c in the EA group (p < 0.05). EA improved the overall morphology and area of pancreatic islets, increased the number of β-cell nuclei, and alleviated β-cell hypertrophy. The abundance of operational taxonomic units (OTUs) in the EA group increased than the model group (p < 0.05), and EA upregulated the Shannon, Chao1, and Ace indices (p < 0.05). EA increased the concentrations of acetic acid, butyric acid, and GLP-1 (p < 0.05). Correlation analysis revealed negative associations between Lactobacillaceae (R = −0.81, p = 0.015) and Lactobacillus (R = −0.759, p = 0.029) with FBG. Peptostreptococcaceae and Romboutsia were negatively correlated with HbA1c (R = −0.81, p = 0.015), while Enterobacteriaceae was positively correlated with OGTT (R = 0.762, p = 0.028). GLP-1 was positively correlated with acetic acid (R = 0.487, p = 0.001), butyric acid (R = 0.586, p = 0.000), isovaleric acid (R = 0.374, p = 0.017), valeric acid (R = 0.535, p = 0.000), and caproic acid (R = 0.371, p = 0.018). Antibiotics disrupted the intestinal microbiota structure and weakened the therapeutic effects of EA.Conclusion: EA effectively improved glucose metabolism in T2DM rats. The hypoglycemic effects of EA were associated with the regulation of gut microbiota, SCFAs, and GLP-1.
研究领域:
医学
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糖尿病研究
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微生物学
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代谢组学
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针灸疗法
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Minghan Li,Jialin Guo,Jinxin Meng,Xueting Wang,Tianxu Pan,Dongyu Zhao,Hongye Li,Ruyi Gao,Ya Wang,Hechun Li,Songyang Li,Jiagan Wang,Haibin Huang,Nan Wang,Shuyuan Yu,Jiayao Guan,Mingxiao Liu,Chunfeng Wang,Guilian Yang
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by inflammation and immune dysregulation, with the gut–liver axis playing a crucial role in immunometabolic balance. While dietary fibers show therapeutic potential, their mechanisms in T2DM remain unclear. This study investigates the effects of synbiotic intervention combining inulin and Lactiplantibacillus plantarum LPm77 on T2DM, focusing on the gut–liver axis. After 7 weeks of synbiotic treatment, significant improvements in hyperglycemia, insulin resistance, and hepatic steatosis were observed in T2DM mice. Inulin promoted L. plantarum LPm77 colonization, enhancing the gut microbiota balance and restoring the intestinal barrier function. It also regulated bile acid levels in the enterohepatic circulation. The synbiotic promoted tauro-ursodeoxycholic acid (TUDCA) biosynthesis, improving hepatic lipid metabolism and activating TGR5. TGR5 activation suppressed M1 macrophage polarization via the TGR5-TLR4-NF-κB pathway, reducing pro-inflammatory cytokines and increasing IL-10, thus alleviating systemic inflammation. This study highlights a novel therapeutic approach targeting immune-metabolic dysregulation in T2DM.
研究领域:
微生物学
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内分泌学
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免疫学
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代谢紊乱
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营养学
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胃肠病学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Journal of Bioresources and Bioproducts
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2025
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IF 13
Shuang Qi,Hui Yang,Tian Fang,Tingwei Zhang,Bo Jiang,Sehrish Manan,Chaofeng Zhang,Peng Wang,Caoxing Huang,Wenjuan Wu,Yongcan Jin
Lignin, a natural and renewable aromatic biopolymer, has gained attention in various biomedical applications due to its diverse structure, excellent biocompatibility, and antioxidant activity. However, the effects of lignin with tailored molecular weight on treating type 2 diabetes mellitus (T2DM) remain largely unexplored. In this study, a series of heterogeneous natural phenolic kraft lignin (KL) with tailored molecular weights, derived through an anti-sugar strategy, were prepared by continuous fractionation. The lignin fractions were categorized as F1, F2, and F3, corresponding to high, medium, and low molecular weights, respectively. Their therapeutic effects on T2DM were evaluated using a fractionated lignin culture cell model and intravenous injection into the tail vein of diabetic rats. The results demonstrated that lignin's protective effects in attenuating T2DM progression were molecular weight-dependent. Specifically, F3 reduced fasting blood glucose, reversed insulin resistance, and improved insulin sensitivity by mitigating oxidative stress and inflammatory responses. Mechanistic investigations revealed that F3 positively regulated glucose and lipid metabolism, inhibited hepatic gluconeogenesis, and enhanced hepatic glycogen synthesis by activating the insulin receptor substrate 1/phosphoinositide 3-kinase/protein kinase B (IRS1/PI3K/AKT) signaling pathway. Results revealed that lignin exerts its therapeutic effects on T2DM in a molecular weight-dependent manner, with IRS1/PI3K/AKT signaling as a potential underlying mechanism. This highlights lignin with a defined molecular weight as a promising candidate for T2DM treatment.
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DOI
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Meng-han Qi,Hai-yan Zhang,Yun-yi Hou,Ivan Steve Nguepi Tsopmejio,Wei Liu,Wen-guang Chang,Chen Chen,Zi Wang,Wei Li
Introduction Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear. Objectives To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment. Methods The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics. Results GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro . Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia. Conclusion This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.
研究领域:
药理学
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内分泌学
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代谢学
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微生物学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Wenwen Liu,Miao Li,Songyi Lin,Tongtong Shi,Yoshimasa Nakamura,Liang Song,Yue Tang
This study developed an emulsion delivery system using fish skin gelatin (FSG) and pectin (PEC) as complex emulsifiers to encapsulate benzyl isothiocyanate (BITC). The stability and BITC release profile of the FSG-PEC emulsion were evaluated in vitro and in vivo . Results indicated that the FSG-PEC emulsion significantly enhanced BITC bioavailability compared to water emulsion and single emulsifier systems, achieving targeted delivery. The BITC-loaded FSG-PEC emulsion significantly increased high-density lipoprotein cholesterol levels, reduced low-density lipoprotein cholesterol, cholesterol, and triglyceride levels, alleviated liver enzyme injuries, lowered creatinine and blood urea nitrogen levels, relieved oxidative stress induced by hyperglycemia, enhanced liver antioxidant capacity, reduced pro-inflammatory factor content in the liver, and improved liver tissue and islet damage in T2DM mice. This research not only provides a theoretical foundation for the delivery and controlled release of lipophilic active substances but also lays the groundwork for further exploration of their functional activities in vivo .
研究领域:
食品科学
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药学
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营养学
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生物技术
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医学研究
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产品关联
DOI
PubMed
高影响因子
BMC Pharmacology & Toxicology
·
2024
·Vol. 25
·期 1
·1-15
·
IF 2.8
Wang Tianyan,Tao Ting,Liu Yi,Dong Jie,Ni Shanhong,Liu Yun,Li Yanli,Xu Ning,Sun Zengxian
Background and purposes It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect. Methods First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX. Results A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal E max model and sigmoidal E max with E 0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration ( T max =0.11 h, t 1/2, ka =0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC 50 , EC 50, 5−OH SAX =0.46EC 50, SAX(parent) , it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature. Conclusions The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.
研究领域:
药理学
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药代动力学
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药效学
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糖尿病研究
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分析化学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 11
·9740-9751
·
IF 4.171
Cheng-Ying Wu,Jing Zhou,Fang Long,Wei Zhang,Hong Shen,He Zhu,Jin-Di Xu,Song-Lin Li
In the present study, the hypoglycemic effects of glucomannan (AGM) and its enzyme-degraded products from Amorphophallus albus were investigated. Four degraded products were prepared through ultrafiltration of β-glucanase-degraded products of AGM. The hypoglycemic activities were evaluated in HFD-STZ-induced type 2 diabetes mellitus (T2DM) mice, and the diversity of gut bacteria was analyzed by 16S rRNA gene sequencing; the fecal short chain fatty acids (SCFAs) and endogenous metabolites were determined by UPLC-QTOF-MS/MS. It was found that AGM and its enzyme-degraded products, though with different molecular weights, had similar β-glycosidic bonds and monosaccharide compositions, exerted similar strength of hypoglycemic effects, and reinstated with a similar extent the disordered gut microbiota and the contents of SCFAs and endogenous metabolites. It was speculated that the hypoglycemic activity of AGM is decided by not the molecular weight but the glycosidic bonds/monosaccharide composition of AGM, which might be structurally specific to the gut bacteria, and thus certain SCFAs and endogenous metabolites that are related to the occurrence and therapy of T2DM. This study provides a scientific basis for using AGM as potential prebiotics beneficial for prevention or therapeutic treatment of T2DM.
研究领域:
营养学
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药理学
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微生物学
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代谢组学
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糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2013
·
IF 3.01
Lihua Jiao,Xin Zhang,Lianqi Huang,Hao Gong,Biao Cheng,Yue Sun,Yixuan Li,Qi Liu,Ling Zheng,Kun Huang
Cinnamon consumption has been found to associate with the attenuation of diabetes mellitus. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as a causative factor of type 2 diabetes mellitus (T2DM). Here, we investigated whether cinnamon has any beneficial effect on the toxic aggregation of hIAPP. We found that cinnamon water extract (CWE) inhibited the amyloid formation of hIAPP in a dose-dependent manner, and identified proanthocyanidins as the major anti-amyloidogenic compounds of CWE. Proanthocyanidins affected the secondary structures of hIAPP and delayed the structural transition from unstructured coils to β-sheet-rich structures. Further studies showed that proanthocyanidins not only inhibited the formation of hIAPP oligomers, but also significantly attenuated the membrane damaging and cytotoxic effects caused by the hIAPP aggregation. Together, these results suggest a possible way by which cinnamon shows beneficial effects on T2DM, and indicate a potential pharmacological usage of proanthocyanidins as an anti-diabetic drug candidate.
研究领域:
药理学
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糖尿病研究
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Ye Ming,Xinyi He,Zhenxing Zhao,Xuehuan Meng,Ye Zhu,Hao Tan,Guoyin Yang,Yun Hu,Leilei Zheng
Purpose Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects.Methods Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis.Results Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats.Conclusion Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.
研究领域:
药理学
·
材料科学
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再生医学
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口腔科学
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细胞生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2022
·Vol. 10
·期 7
·2455-2469
·
IF 3.553
Xiaoyu Chen,Hongyuan Zhao,Fanqiang Meng,Libang Zhou,Xinyi Pang,Zhaoxin Lu,Yingjian Lu
Surfactin, produced by Bacillus amyloliquefaciens fmb50, was used to treat insulin-resistant (IR) hepatocyte. It was found that surfactin increased glucose consumption in insulin-resistant HepG2 (IR-HepG2) cells and ameliorated IR by increasing glucose transporter 4 (GLUT4) protein expression and AMP-activated protein kinase (AMPK) mRNA expression, promoting GLUT4 translocation and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in IR-HepG2 cells. Meanwhile, surfactin downregulated protein expression of phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase), further inhibiting hepatic gluconeogenesis. In addition, surfactin played important roles in eliminating reactive oxygen species (ROS), improving mitochondrial dysfunction, and inhibiting proinflammatory mediators. We observed that surfactin promoted glucose consumption, meanwhile increased translocation and protein expression of GLUT4 in Caco-2 cells. These results confirmed the conclusion in hepatic cells. Furthermore, surfactin supplement decreased body weight, food intake, and fasting blood glucose of type 2 diabetes mellitus (T2DM) mice induced by streptozotocin (STZ)/high-fat diet (HFD). Our data indicated that surfactin ameliorated insulin resistance and lowered blood glucose in intro and in vivo.
研究领域:
药理学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）