Although body mass index(BMI)is widely used as a simple tool to assess obesity,it has certain limitations and inaccuracies.It is known that visceral adipose tissue is closely related to cardiometabolic risks and all-c...Although body mass index(BMI)is widely used as a simple tool to assess obesity,it has certain limitations and inaccuracies.It is known that visceral adipose tissue is closely related to cardiometabolic risks and all-cause mortality;however,precise measurement methods for visceral fat(magnetic resonance imaging and computed tomography)cannot be widely used.Thus,simple but accurate alternatives are valuable.Studies have shown that waist circumference-to-height ratio(WHtR)might be a superior and more accurate variable in assessing central or visceral adiposity as well as predicting risks of diabetes and other cardiometabolic diseases.Furthermore,WHtR cutoff values can be consistent across different races,age,and genders,making it a universal metric worth promoting and applying.展开更多
OBJECTIVE To investigate the role of active component of Isatidis Radix on insulin resistance in the diabetes mellitus rat.METHODS To induce diabetic rat model with long-term high sugar and high fat plus low-dose stre...OBJECTIVE To investigate the role of active component of Isatidis Radix on insulin resistance in the diabetes mellitus rat.METHODS To induce diabetic rat model with long-term high sugar and high fat plus low-dose streptozotocin(25 mg·kg-1).Then rats were randomly divided into 6 groups:control group,model group,rosiglitazone maleate group(0.3mg·kg-1),high(100mg·kg-1),middle(50mg·kg-1)and low(25 mg·kg-1)active component of Isatidis Radix group.Drugs were adiministered orally once a day.After four weeks,following substances were measured:serum fasting blood glucose,total cholesterol,triglycerides,high density lipoprotein,low density lipoprotein,free fatty acids,fasting insulin,insulin index,pathological observation and immunohistochemistry technology of pancreas islet.RESULTS High and middle active component of Isatidis Radix group could decrease serum FBG,TC,TG,LDL,FFA,FINS and increase serum HDL,ISI;the damage of the pancreas islet has been restoration partly.CONCLUSION Active component of Isatidis Radix could improve insulin resistance in diabetic rats,which might be related to improvement of the function of pancreas islet.展开更多
Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholest...Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholesterolemia(FH)is less determined.The current study aims to characterize the clinical,laboratory,coronary and genetic characteristics of the FH patients with T2DM compared with FH alone.展开更多
Objective It remains undetermined whether biodegradable polymer drug-eluting stents(BP-DES)are superior to second generation drugeluting stents(G2-DES)in patients with and without diabetes mellitus(DM).The study aims ...Objective It remains undetermined whether biodegradable polymer drug-eluting stents(BP-DES)are superior to second generation drugeluting stents(G2-DES)in patients with and without diabetes mellitus(DM).The study aims to evaluate the efficacy and safety of G2-DES and BP-DES in patients with and without DM in a high-volume cardiovascular center in China.展开更多
目的探讨2型糖尿病患者伴有的抑郁障碍。方法采用北京大学PES心理应用系统中汉密顿抑郁量表(HRSD)对62例2型糖尿病患者(有并发症者32例,无并发症者30例)及20名健康人进行评定,并对HRSD 的7 类因子进行分析。结果糖尿病组的HRSD总分均高...目的探讨2型糖尿病患者伴有的抑郁障碍。方法采用北京大学PES心理应用系统中汉密顿抑郁量表(HRSD)对62例2型糖尿病患者(有并发症者32例,无并发症者30例)及20名健康人进行评定,并对HRSD 的7 类因子进行分析。结果糖尿病组的HRSD总分均高于正常对照组,且糖尿病有并发症组高于无并发症组( P <0.05)。糖尿病组的焦虑/躯体化、认知障碍因子分均高于正常对照组,且糖尿病有并发症组的迟缓、睡眠障碍因子分高于正常对照组( P <0.05),而无并发症组与正常对照组无显著性差异( P >0.05)。在日夜变化、体重、绝望感方面,糖尿病组与正常对照组无显著性差异( P >0.05)。结论糖尿病患者伴有抑郁障碍,且有并发症患者明显重于无并发症患者。展开更多
OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and th...OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.展开更多
Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKak...Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKakizaki(GK)rat is a nonobese,nonhypertensive model of type 2 diabetes,which,like humans,shares a susceptibility locus on chromosome 10[4-5].展开更多
A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthe...A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthesized by the chemical reactions between vitamin D3(VD3), VOSO4 and amino acids(AAn) with equal molar ratio 1∶1∶1 in neutralized media. The structures of these complexes were elucidated by spectroscopic methods like, infrared and solid reflectance spectroscopes. Magnetic moments and electronic spectra reveal square pyramid geometrical structure of the complexes. The infrared spectra assignments of these complexes revealed that the chelation towards vanadyl(Ⅳ) ions existed via deprotonation of the hydroxyl group of VD3 drug ligand and so amino acids act as bidentate ligand via N-amino and O-carboxylate groups. The anti-diabetic efficiency of these complexes were evaluated against streptozotocin induced diabetic male albino rats.展开更多
Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further su...Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.展开更多
OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or ...OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.展开更多
Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading t...Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.展开更多
OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics ...OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics was associated with the increased reactive oxygen species(ROS)production in endothelial cells,which is a significant contributor to the microvascular complications of diabetes.The present study was designed to determine the involvement of transcription factor FOXO1in diabetic wound healing and investigate underlying mechanisms.METHODS&RESULTS Impaired mitochondrial networks and increased phosphorylation of dynaminrelated protein-1(Drp1)at ser616,a protein required for mitochondrial fission,were observed in human umbilical vein endothelial cells(HUVECs)24 h after exposure to high concentrations of glucose.Inhibition of FOXO1 by si RNA or by FOXO1 selective inhibitor AS1842856 abrogated high glucos-induced alterations in mitochondrial networks and phosphorylation of Drp1.Treatment with AS1842856 or si RNA of FOXO1 could significantly increase the mitochondrial membrane potential and suppress the overproduction of ROS induced by high glucose.Addition of AS1842856 inhibited glucoseinduced apoptosis,ameliorated capillary tube formation in HUVECs.In vivo,AS1842856 dose-dependently rescued the delay of wound closure in diabetic mice,and5 mg·kg-1of AS1842856 treatment significantly increased the mean perfusion rate.CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in endothelial cells,inhibition of FOXO1 rescued the delayed wound healing and improved wound angiogenesis in diabetic mice.展开更多
OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the pr...OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.展开更多
基金supported by the“1·3·5 Project”for Disciplines of Excellence,West China Hospital,Sichuan University,China(ZYGD18017)。
文摘Although body mass index(BMI)is widely used as a simple tool to assess obesity,it has certain limitations and inaccuracies.It is known that visceral adipose tissue is closely related to cardiometabolic risks and all-cause mortality;however,precise measurement methods for visceral fat(magnetic resonance imaging and computed tomography)cannot be widely used.Thus,simple but accurate alternatives are valuable.Studies have shown that waist circumference-to-height ratio(WHtR)might be a superior and more accurate variable in assessing central or visceral adiposity as well as predicting risks of diabetes and other cardiometabolic diseases.Furthermore,WHtR cutoff values can be consistent across different races,age,and genders,making it a universal metric worth promoting and applying.
基金The project supported by Spark Technology Project by Jiangsu Province(BE2004339)
文摘OBJECTIVE To investigate the role of active component of Isatidis Radix on insulin resistance in the diabetes mellitus rat.METHODS To induce diabetic rat model with long-term high sugar and high fat plus low-dose streptozotocin(25 mg·kg-1).Then rats were randomly divided into 6 groups:control group,model group,rosiglitazone maleate group(0.3mg·kg-1),high(100mg·kg-1),middle(50mg·kg-1)and low(25 mg·kg-1)active component of Isatidis Radix group.Drugs were adiministered orally once a day.After four weeks,following substances were measured:serum fasting blood glucose,total cholesterol,triglycerides,high density lipoprotein,low density lipoprotein,free fatty acids,fasting insulin,insulin index,pathological observation and immunohistochemistry technology of pancreas islet.RESULTS High and middle active component of Isatidis Radix group could decrease serum FBG,TC,TG,LDL,FFA,FINS and increase serum HDL,ISI;the damage of the pancreas islet has been restoration partly.CONCLUSION Active component of Isatidis Radix could improve insulin resistance in diabetic rats,which might be related to improvement of the function of pancreas islet.
文摘Background Though type 2 diabetes mellitus(T2DM)is an important and independent risk factor for coronary artery disease(CAD)in general population,whether this feature also exists in patients with familial hypercholesterolemia(FH)is less determined.The current study aims to characterize the clinical,laboratory,coronary and genetic characteristics of the FH patients with T2DM compared with FH alone.
文摘Objective It remains undetermined whether biodegradable polymer drug-eluting stents(BP-DES)are superior to second generation drugeluting stents(G2-DES)in patients with and without diabetes mellitus(DM).The study aims to evaluate the efficacy and safety of G2-DES and BP-DES in patients with and without DM in a high-volume cardiovascular center in China.
文摘目的探讨2型糖尿病患者伴有的抑郁障碍。方法采用北京大学PES心理应用系统中汉密顿抑郁量表(HRSD)对62例2型糖尿病患者(有并发症者32例,无并发症者30例)及20名健康人进行评定,并对HRSD 的7 类因子进行分析。结果糖尿病组的HRSD总分均高于正常对照组,且糖尿病有并发症组高于无并发症组( P <0.05)。糖尿病组的焦虑/躯体化、认知障碍因子分均高于正常对照组,且糖尿病有并发症组的迟缓、睡眠障碍因子分高于正常对照组( P <0.05),而无并发症组与正常对照组无显著性差异( P >0.05)。在日夜变化、体重、绝望感方面,糖尿病组与正常对照组无显著性差异( P >0.05)。结论糖尿病患者伴有抑郁障碍,且有并发症患者明显重于无并发症患者。
基金The project supported by National Natural Science Foundation of China(81373460)by the Natural Science Foundation of Guangdong Province(2014A030313744)
文摘OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.
基金supported by a grant from Beijing Brain Project(Z161100000217141)。
文摘Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKakizaki(GK)rat is a nonobese,nonhypertensive model of type 2 diabetes,which,like humans,shares a susceptibility locus on chromosome 10[4-5].
文摘A new six intraperitoneal injection insulin-mimetic vanadyl(Ⅱ) compounds [(VD3^-1)(VO^+2)(AAn^-1)](where(n=1~6);AA1=isoleucine, AA2=threonine, AA3=proline, AA4=phenylalanine, AA5=lysine and AA6=glutamine) were synthesized by the chemical reactions between vitamin D3(VD3), VOSO4 and amino acids(AAn) with equal molar ratio 1∶1∶1 in neutralized media. The structures of these complexes were elucidated by spectroscopic methods like, infrared and solid reflectance spectroscopes. Magnetic moments and electronic spectra reveal square pyramid geometrical structure of the complexes. The infrared spectra assignments of these complexes revealed that the chelation towards vanadyl(Ⅳ) ions existed via deprotonation of the hydroxyl group of VD3 drug ligand and so amino acids act as bidentate ligand via N-amino and O-carboxylate groups. The anti-diabetic efficiency of these complexes were evaluated against streptozotocin induced diabetic male albino rats.
文摘Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.
基金The project supported by National Natural Science Foundation of China(81370339)Promotion Project of Beijing Education Committee(TJSHJ201510025005)
文摘OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.
文摘Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.
基金The project supported by National Natural Science Foundation of China(81373405,30901803)Beijing Higher Education Young Elite Teacher Project(YETP0053)
文摘OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens.Recent studies have shown that the imbalance of mitochondrial dynamics was associated with the increased reactive oxygen species(ROS)production in endothelial cells,which is a significant contributor to the microvascular complications of diabetes.The present study was designed to determine the involvement of transcription factor FOXO1in diabetic wound healing and investigate underlying mechanisms.METHODS&RESULTS Impaired mitochondrial networks and increased phosphorylation of dynaminrelated protein-1(Drp1)at ser616,a protein required for mitochondrial fission,were observed in human umbilical vein endothelial cells(HUVECs)24 h after exposure to high concentrations of glucose.Inhibition of FOXO1 by si RNA or by FOXO1 selective inhibitor AS1842856 abrogated high glucos-induced alterations in mitochondrial networks and phosphorylation of Drp1.Treatment with AS1842856 or si RNA of FOXO1 could significantly increase the mitochondrial membrane potential and suppress the overproduction of ROS induced by high glucose.Addition of AS1842856 inhibited glucoseinduced apoptosis,ameliorated capillary tube formation in HUVECs.In vivo,AS1842856 dose-dependently rescued the delay of wound closure in diabetic mice,and5 mg·kg-1of AS1842856 treatment significantly increased the mean perfusion rate.CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in endothelial cells,inhibition of FOXO1 rescued the delayed wound healing and improved wound angiogenesis in diabetic mice.
基金supported by National Nature Science Foundation of China(81770847)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-3-007,2016-I2M-1-010)National Key Research and Development Plan(2016YFC1000905)
文摘OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.
