Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chro...Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.展开更多
AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabet...AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.展开更多
Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrost...Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.展开更多
Recent studies have confirmed thatβ-adrenergic receptors(β-ARs)are expressed on the surface of osteoblasts and osteoclasts,and that the sympathetic nervous system can regulate bone metabolism by activating them.β-A...Recent studies have confirmed thatβ-adrenergic receptors(β-ARs)are expressed on the surface of osteoblasts and osteoclasts,and that the sympathetic nervous system can regulate bone metabolism by activating them.β-AR blockers(BBs)are commonly used in the treatment of cardiovascular diseases in the elderly.It is important to investigate whether BBs have a beneficial effect on bone metabolism in the treatment of cardiovascular diseases,so as to expand their clinical application.This article reviews the effects of BB on bone metabolism and the progress of clinical research.展开更多
Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic recept...Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.展开更多
目的探讨β1受体阻滞剂艾司洛尔(Esmolol)能否上调血红素氧合酶-1(heme oxygenase-1,HO-1)起到对脓毒症大鼠肠道功能的保护作用。方法本实验于哈尔滨医科大学附属第一医院外科中心实验室完成。40只雄性Wistar大鼠按随机数字表法分为4组...目的探讨β1受体阻滞剂艾司洛尔(Esmolol)能否上调血红素氧合酶-1(heme oxygenase-1,HO-1)起到对脓毒症大鼠肠道功能的保护作用。方法本实验于哈尔滨医科大学附属第一医院外科中心实验室完成。40只雄性Wistar大鼠按随机数字表法分为4组:假手术组(sham组,n=10)、脓毒症组(CLP组,n=10)、艾司洛尔干预组(Esmolol+CLP组,n=10)、HO-1抑制剂组(Esmolol+Zn PP+CLP组,n=10)。采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型,Esmolol组通过静脉输注艾司洛尔注射液,速度为15mg/(kg·h),Esmolol+Zn PP+CLP组术前1h腹腔内注射Zn PP溶液(40μmol/kg),术后同速静脉输注艾司洛尔注射液。其余各组大鼠腹腔注射等体积生理盐水,并且静脉输注等渗盐水,速度2ml/(kg·h)。术后12h处死大鼠,ELISA法检测各组血清肿瘤坏死因子(TNF-α)和白细胞介素(IL-1β)水平,采用蛋白印迹法及免疫组化法检测大鼠肠组织HO-1表达水平,光学显微镜观察大鼠肠组织病理变化情况。结果与Sham组相比,CLP组大鼠血清TNF-α、IL-1β水平均明显升高(43.71±6.24pg/ml vs 2742.69±221.71pg/ml,52.69±14.15pg/ml vs 482.73±125.49pg/ml,P<0.05);肠组织中HO-1水平表达升高(P<0.05);肠组织病理损伤明显。与CLP组相比,Esmolol+CLP组血清TNF-α、IL-1β水平均明显下降(2742.69±221.71pg/ml vs 968.81±99.46pg/ml,482.73±125.49pg/ml vs 156.15±38.29pg/ml,P<0.05);肠组织HO-1水平表达明显升高(P<0.05);肠组织病理损伤程度减轻。与CLP组相比,Esmolol+Zn PP+CLP组大鼠血清TNF-α、IL-1β水平无明显差异(2742.69±221.71pg/ml vs 2545.18±173.74pg/ml,482.73±125.49pg/ml vs 474.43±113.98pg/ml,P>0.05);肠组织病理损伤程度无明显差异。结论 Esmolol能改善脓毒症诱发的肠道损伤,其可能是通过上调HO-1通路来减轻肠组织炎性反应,继而减轻肠道损伤。展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) tran...Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.展开更多
文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.
基金Supported by Biomedical Research Institute Grant(PNU-2013-0373),Pusan National University Hospital
文摘AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.
文摘Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as cases.For each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian treatment.Binary logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs use.Ninety-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian treatment.The mean UPDRS part III score was 18.87±7.6 and the median HY stage was 2.In the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/ARBs.Conversely,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between groups.After controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.The study was approved by the Ethics Committee of Novara University Hospital“Maggiore della Carità”(CE 65/16)on July 27,2016.
基金Supported by National Natural Sciences Foundation of China,No.81200649Natural Sciences Foundation of Hubei Province of China,No.2016CFB425Fundamental Research Funds for the Central University,No.2016YXMS236.
文摘Recent studies have confirmed thatβ-adrenergic receptors(β-ARs)are expressed on the surface of osteoblasts and osteoclasts,and that the sympathetic nervous system can regulate bone metabolism by activating them.β-AR blockers(BBs)are commonly used in the treatment of cardiovascular diseases in the elderly.It is important to investigate whether BBs have a beneficial effect on bone metabolism in the treatment of cardiovascular diseases,so as to expand their clinical application.This article reviews the effects of BB on bone metabolism and the progress of clinical research.
文摘Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.
文摘目的探讨β1受体阻滞剂艾司洛尔(Esmolol)能否上调血红素氧合酶-1(heme oxygenase-1,HO-1)起到对脓毒症大鼠肠道功能的保护作用。方法本实验于哈尔滨医科大学附属第一医院外科中心实验室完成。40只雄性Wistar大鼠按随机数字表法分为4组:假手术组(sham组,n=10)、脓毒症组(CLP组,n=10)、艾司洛尔干预组(Esmolol+CLP组,n=10)、HO-1抑制剂组(Esmolol+Zn PP+CLP组,n=10)。采用盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型,Esmolol组通过静脉输注艾司洛尔注射液,速度为15mg/(kg·h),Esmolol+Zn PP+CLP组术前1h腹腔内注射Zn PP溶液(40μmol/kg),术后同速静脉输注艾司洛尔注射液。其余各组大鼠腹腔注射等体积生理盐水,并且静脉输注等渗盐水,速度2ml/(kg·h)。术后12h处死大鼠,ELISA法检测各组血清肿瘤坏死因子(TNF-α)和白细胞介素(IL-1β)水平,采用蛋白印迹法及免疫组化法检测大鼠肠组织HO-1表达水平,光学显微镜观察大鼠肠组织病理变化情况。结果与Sham组相比,CLP组大鼠血清TNF-α、IL-1β水平均明显升高(43.71±6.24pg/ml vs 2742.69±221.71pg/ml,52.69±14.15pg/ml vs 482.73±125.49pg/ml,P<0.05);肠组织中HO-1水平表达升高(P<0.05);肠组织病理损伤明显。与CLP组相比,Esmolol+CLP组血清TNF-α、IL-1β水平均明显下降(2742.69±221.71pg/ml vs 968.81±99.46pg/ml,482.73±125.49pg/ml vs 156.15±38.29pg/ml,P<0.05);肠组织HO-1水平表达明显升高(P<0.05);肠组织病理损伤程度减轻。与CLP组相比,Esmolol+Zn PP+CLP组大鼠血清TNF-α、IL-1β水平无明显差异(2742.69±221.71pg/ml vs 2545.18±173.74pg/ml,482.73±125.49pg/ml vs 474.43±113.98pg/ml,P>0.05);肠组织病理损伤程度无明显差异。结论 Esmolol能改善脓毒症诱发的肠道损伤,其可能是通过上调HO-1通路来减轻肠组织炎性反应,继而减轻肠道损伤。
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
基金supported by the Postdoctoral Fellow Foundation of the Science and Technology Committee of Shanghai (No. 98-10)the Natural Science Foundation of Chinese People's Armed Police Force (Nos. WKH2006-5 and WKH2008ZO4), China
文摘Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.
