JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2022
·Vol. 36
·期 4
·e24350
·
IF 3.124
Fenghui Pan,Wenxia Cui,Lei Gao,Xiaoting Shi,Haiyan Yang,Yun Hu,Man Li
Objective To investigate the relationship between serum lutein and type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) in elderly individuals. Methods A total of 60 T2DM patients over 60 years were subgrouped into a DKD group and a non-DKD group according to their urinary microalbumin-to-creatinine ratio (UACR), while 30 age-matched non-T2DM patients were recruited in the control group. Baseline characteristics, laboratory examination results, and serum lutein levels were compared, and their correlations were analyzed. Receiver operating characteristic (ROC) curves were plotted to identify the diagnostic potential of lutein in T2DM and DKD. Results The lutein level in the T2DM group was significantly lower than that in the control group and was also significantly lower in the DKD group than in the non-DKD group ( p < 0.001). Lutein levels were negatively correlated with body mass index, glycosylated hemoglobin, fasting blood glucose, triglyceride, and UACR and positively correlated with high-density lipoprotein cholesterol ( p < 0.05). T2DM patients were divided into four groups according to the quartile of their lutein level. The proportion of T2DM and DKD gradually decreased with increasing lutein levels ( p < 0.001). The area under the ROC curve of serum lutein in diagnosing T2DM and DKD was 0.880 and 0.779, respectively, with corresponding cut-off values of 0.433 μmol/L and 0.197 μmol/L ( p < 0.001). Conclusion The serum level of lutein is negatively correlated with the incidence of T2DM and DKD in the elderly and can serve as a diagnostic marker for T2DM and DKD.
研究领域:
医学
·
内分泌学
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老年医学
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产品关联
DOI
PubMed
高影响因子
Cardiovascular Diabetology
·
2024
·Vol. 23
·期 1
·1-19
·
IF 8.5
Tang Yuan-juan,Zhang Zhen,Yan Tong,Chen Ken,Xu Guo-fan,Xiong Shi-qiang,Wu Dai-qian,Chen Jie,Jose Pedro A.,Zeng Chun-yu,Fu Jin-juan
Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. Methods and results T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. Conclusion This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
研究领域:
内分泌学
·
心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 57
·35994-36006
·
IF 3.361
Jiale Cai,Xiaoting Zhong,Jiayin Liang,Can Xu,Huanzheng Yu,Minghua Xian,Chunyan Yan,Shumei Wang
Diabetes seriously endangers public health and brings a heavy economic burden to the country. Inflammation is one of the main inducing factors of type-2 diabetes (T2D) and may cause some complications of diabetes, such as diabetic encephalopathy and peripheral neuropathy. In-depth research and development of drugs to cure diabetes and complications are of great significance. Pueraria lobate is a medicinal herb used in several countries to treat many diseases. Here, two new polysaccharides (PLB-1-1 and PLB-1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9.1 × 103 Da and 3.8 × 103 Da, respectively. The structure was evaluated by monosaccharide composition, GC-MS and NMR spectroscopy. It was determined that PLB-1-1 comprised →4)-α-D-Glcp-(1→, α-D-Glcp-(1→, →6)-β-D-Galp-(1→, →3)-α-L-Araf-(1→, →3,6)-β-D-Manp-(1→ and →4,6)-β-D-Manp-(1→, and PLB-1-2 consisted of →4)-α-D-Glcp-(1→, β-D-Glcp-(1→, →4,6)-β-D-Glcp-(1→, →3,6)-β-D-Manp-(1→ and α-L-Fucp-(1→. Furthermore, both PLB-1-1 and PLB-1-2 showed anti-inflammatory and inhibitory activities of α-glucosidase and α-amylase in vitro. Therefore, the new polysaccharides, i.e., PLB-1-1 and PLB-1-2, may be considered candidates for the treatment of diabetes and its related complications.
研究领域:
药理学
·
生物化学
·
糖尿病研究
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Huishang Yang,Chen Lai,Chengkai Xuan,Muyuan Chai,Xuemin Liu,Yunhua Chen,Xuetao Shi
Diabetics face multiple long-term health complications and diabetic foot ulcers affect approximately 15–20% of the diabetic population. The high disability rate of these patients results in substantial mental burden and economic pressure to the individuals as well as the societies. Here, we report a therapeutic integrin-binding pro-survival peptide-engineered silk fibroin nanosheet that can regulate angiogenesis and promote diabetic ulcer healing. The nanosheet with thickness less than 100 nm is highly transparent and flexible, and it can firmly adhere to the biological tissue surfaces in underwater environment. The presence of integrin-binding pro-survival peptide in the nanosheet significantly upregulates the expression of angiogenesis genes and proteins of human umbilical vein endothelial cells (HUVECs). In the diabetic mouse model, the peptide-engineered nanosheet reveals significant acceleration of wound closure, epithelialization and granulation tissue formation. These findings suggest that this functional nanosheet could be a promising therapeutic candidate for complicated diabetic ulcer healing.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
糖尿病研究
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Zhi Lu,Yiqun Yao,Jinhong Wang,J.-Y. Peng
Dioscin presents extents of pharmacological activities on several diseases, but its effect and mechanism on diabetes cognitive dysfunction (DCD) remains unclear. Herein, we conducted a series of pharmacological evaluation assays of purinergic receptor P2X7 (P2X7R) with dioscin. We uncovered that dioscin presented a clearly protective effect on diabetes cognitive dysfunction via a methylglyoxal-treated PC12 cell model and streptozocin (STZ)-induced rat models. Additionally, it found that P2X7R and NLRP3 inflammasome signals were activated in diabetes cognitive dysfunction via in vivo and in vitro detection. Moreover, it was demonstrated that P2X7R regulated NLRP3 inflammasome signals in methylglyoxal-treated PC12 cells. Meanwhile, it was showed that dioscin-induced anti-diabetes cognitive dysfunction effect was accompanied with an inhibition of P2X7R/NLRP3 signal. A deeper mechanical study indicated that an overexpression of P2X7R further enhanced the protective effect of dioscin. Whilst, an inhibition of P2X7R abolished the protective effect of dioscin. These results suggested that dioscin protected type 2 diabetes cognitive dysfunction through, at least partially, regulating the P2X7R/NLRP3 signal pathway. Our findings further indicate the great value of dioscin on preventing type 2 diabetes cognitive dysfunction.
研究领域:
药理学
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神经科学
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糖尿病
·
炎症
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产品关联
DOI
PubMed
高影响因子
World Journal of Diabetes
·
2025
·Vol. 16
·期 2
·93130
·
IF 4.6
Chong-Xi Yuan,Xuan Wang,Yun Liu,Tian-Cheng Xu,Zhi Yu,Bin Xu
BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities. The effects mediated by the silent information regulator type 2 homolog-1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy (T2DPN), potentially breaking this harmful cycle. AIM To validate the effectiveness of electroacupuncture (EA) in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1α axis. METHODS The effects of EA were evaluated through assessments of metabolic changes, morphological observations, and functional examinations of the sciatic nerve, along with measurements of inflammation and oxidative stress. Proteins related to the SIRT1/PGC-1α axis, involved in the regulation of mitochondrial biogenesis and antioxidative stress, were detected in the sciatic nerve using Western blotting to explain the underlying mechanism. A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis. RESULTS In addition to diabetes-related metabolic changes, T2DPN rats showed significant reductions in pain threshold after 9 weeks, suggesting abnormal peripheral nerve function. EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats. The SIRT1/PGC-1α axis, which was downregulated in the model group, was upregulated by EA intervention. The endogenous antioxidant system related to the SIRT1/PGC-1α axis, previously inhibited in diabetic rats, was reactivated. A similar trend was observed in inflammatory markers. When SIRT1 was inhibited in diabetic rats, these beneficial effects were abolished. CONCLUSION EA can alleviate the symptoms of T2DNP in experimental rats, and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1α axis.
研究领域:
神经科学
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内分泌学
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分子生物学
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替代医学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2024
·Vol. 38
·期 17
·e70019
·
IF 4.4
Yuxue Xu,Yue Peng,Xiaojun Wu,Feixue Ni,Daxi Sun,Pengfei Zhang,Yang Yang,Miao Yan,Jia Mi,Geng Tian
Non-proliferative diabetic retinopathy (NPDR) is the early stage of diabetic retinopathy (DR) and is a chronic oxidative stress-related ocular disease. Few treatments are approved for early DR. This study aimed to investigate the pathogenic mechanisms underlying the retinal micro-vasculopathy induced by diabetes and to explore an early potential for treating early DR in a mouse model. The mouse model of type 1 diabetes was established by intraperitoneal injection of streptozotocin (STZ, 180 mg/kg), which was used as the early DR model. The body weight and blood glucose mice were measured regularly; The retinal vascular leakage in the early DR mice was determined by whole-mount staining; Label-free quantitative proteomic analysis and bioinformatics were used to explore the target proteins and signaling pathways associated with the retinal tissues of early DR mice; To detect the effects of target protein on endothelial cell proliferation, migration, and tube formation, knockdown and overexpression of VEGF-B were performed in human retinal vascular endothelial cells (HRECs); Western blotting was used to detect the expression of target proteins in vitro and in vivo; Meanwhile, the therapeutic effect of VEGF-B on vascular leakage has also been evaluated in vitro and in vivo. The protein expressions of vascular endothelial growth factor (VEGF)-B and the Rho GTPases family member CDC42 were reduced in the retinal tissues of early DR. VEGF-B upregulated the expression of CDC42/ZO1/VE-cadherin and prevented hyperglycemia-induced vascular leakage in HRECs. Standard intravitreal VEGF-B injections improved the retinal vascular leakage and neurovascular response in early DR mice. Our findings demonstrated, for the first time, that in diabetes, the retinal vessels are damaged due to decreased VEGF-B expression through downregulation of CDC42/ZO1/VE-cadherin expression. Therefore, VEGF-B could be used as a novel therapy for early DR.
研究领域:
糖尿病
·
眼科学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Nutrients
·
2021
·Vol. 13
·期 12
·4379
·
IF 5.719
Hui Zhou,Yuanyuan Wu,Eunhye Kim,Haibo Pan,Puming He,Bo Li,Yi Charlie Chen,Youying Tu
Theaflavin-3,3′-digallate (TF3) is the most important theaflavin monomer in black tea. TF3 was proved to reduce blood glucose level in mice and rats. However, the elaborate anti-diabetic mechanism was not well elucidated. In this work, human hepatoma G2 (HepG2) cells and zebrafish (Danio rerio) were used simultaneously to reveal anti-diabetic effect of TF3. The results showed that TF3 could effectively rise glucose absorption capacity in insulin-resistant HepG2 cells and regulate glucose level in diabetic zebrafish. The hypoglycemic effect was mediated through down-regulating phosphoenolpyruvate carboxykinase and up-regulating glucokinase. More importantly, TF3 could significantly improve β cells regeneration in diabetic zebrafish at low concentrations (5 μg/mL and 10 μg/mL), which meant TF3 had a strong anti-diabetic effect. Obviously, this work provided the potential benefit of TF3 on hypoglycemic effect, regulating glucose metabolism enzymes, and protecting β cells. TF3 might be a promising agent for combating diabetes.Keywords:theaflavin-3,3′-digallate;anti-diabetic effect;HepG2 cells;diabetic zebrafish model;glucose metabolism enzymes
研究领域:
生物化学
·
医学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CURRENT MOLECULAR MEDICINE
·
2023
·
IF 2.5
Kuang Xinmou,Su Minru,Li Hao,Sheng Xiaolan,Cai Huan,Xie Shuilin,Liu Zhonghua
Background: 3-Amino-4-(2,4,5-trifluorophenyl) butyric acid has potential
pharmacological effects in promoting insulin secretion. Menthol promotes drug
transdermal absorption and hypoglycemic effects.
Objective: The objective of the study was to combine the 3-amino-4-(2,4,5-
trifluorophenyl) butyric acid and menthol to develop a new candidate drug molecule
that can be used as a hypoglycemic drug in type II diabetes.
Methods: In this study, the molecular structure of 3-amino-4-(2,4,5-trifluorophenyl)
butyric acid in sitagliptin was modified by replacing pyrazine imidazole with menthol.
The structure of the target compound was characterized by nuclear magnetic
resonance (NMR). The anti-diabetic activity of BHF in N000180 BKS.Cg-Dock7m+/
+Leprdb/Nju mice with spontaneous diabetes was preliminarily studied.
Results: A potential multi-target drug molecule, 3-amino-4-(2,4,5-trifluorophenyl)
butyrate (BHF), was synthesized by combining 3-amino-4-(2,4,5-trifluorophenyl) butyric
acid and menthol. BHF is suitable for hyperglycemic mice and has a significant
hypoglycemic effect; the low dose of 10 mg/kg-1 started to be effective, and the high
dose of 40 mg/kg-1 was more effective than the positive drug metformin.
Conclusion: In this study, BHF has been synthesized and presented significant
antidiabetic activities.
研究领域:
药理学
·
药物化学
·
代谢病学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jiahan Ke,Jianan Pan,Hao Lin,Shuying Huang,Junfeng Zhang,Changqian Wang,Alex Chia Yu Chang,Jun Gu
Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA-Seq data and Rab7-CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab-interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML-098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7-Rilp-mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested.
研究领域:
心脏病学
·
细胞生物学
·
分子生物学
·
药理学
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2023
·
IF 8.2
Xu Jia-wen,Xu Xu,Ling Yun,Wang Yan-chun,Huang Yu-jie,Yang Juan-zhen,Wang Jia-ying,Shen Xu
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic β-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle , is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg -1 ·d -1 , i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either β-Arrestin2 or β-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKβ/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.
研究领域:
药理学
·
神经科学
·
内分泌学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Zhangnian Liu,Shiquan Gan,Lingyun Fu,Yini Xu,Shengquan Wang,Guangqiong Zhang,Di Pan,Ling Tao,Xiangchun Shen
1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.
研究领域:
药理学
·
眼科学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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