BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions...BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure cont展开更多
Heart failure(HF)is a major global health challenge,particularly among indi-viduals with type 2 diabetes mellitus(T2DM),who are at significantly higher risk of developing HF.Diabetic cardiomyopathy,a unique form of he...Heart failure(HF)is a major global health challenge,particularly among indi-viduals with type 2 diabetes mellitus(T2DM),who are at significantly higher risk of developing HF.Diabetic cardiomyopathy,a unique form of heart disease,often progresses silently until advanced stages.Recent research has focused on sodium-dependent glucose transporter 2 inhibitors(SGLT2i),originally developed for hyperglycemia,which have shown potential in reducing cardiovascular risks,including HF hospitalizations,irrespective of diabetic status.In this editorial we comment on the article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.The investigators examined the effects of SGLT2i on myocardial function in T2DM patients with asymptomatic HF,finding significant improvements in stroke volume index and reductions in systemic vascular resis-tance,suggesting enhanced cardiac output.Additionally,SGLT2i demonstrated anti-inflammatory and antioxidant effects,as well as blood pressure reduction,though the study’s limitations—such as small sample size and observational design—necessitate larger randomized trials to confirm these findings.The study underscores the potential of early intervention with SGLT2i in preventing HF progression in T2DM patients.展开更多
We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent g...We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.展开更多
This article addresses the substantial findings of a study on sodium-dependent glucose transporter 2 inhibitors(SGLT2is)and their effects on myocardial function in patients with type 2 diabetes and asymptomatic heart ...This article addresses the substantial findings of a study on sodium-dependent glucose transporter 2 inhibitors(SGLT2is)and their effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.The editorial explores the broader implications of the study findings for clinical practice,thus highlighting the pivotal role of SGLT2is in improving cardiac function,reducing oxidative stress,and attenuating inflammation.It emphasizes the importance of early intervention with SGLT2is in preventing the progression of diabetic cardio-myopathy;hence,these inhibitors have the potential to transform the manage-ment of asymptomatic heart failure in patients with diabetes.展开更多
Type 2 Diabetes Mellitus (T2DM) is a systemic metabolic disorder with complex pathogenesis. In recent years, a variety of new T2DM drugs have emerged, such as sodium-dependent glucose transporters 2 (SGLT-2) inhibitor...Type 2 Diabetes Mellitus (T2DM) is a systemic metabolic disorder with complex pathogenesis. In recent years, a variety of new T2DM drugs have emerged, such as sodium-dependent glucose transporters 2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. As traditional medicines, insulin also has developed kinds of formulations such as quick-acting or premixed insulin. In addition, new treatment schedules combining multiple drugs are also fully explored. The efficacy, the administration, the mechanism, the safety and the price of these drugs are all different, providing patients with multiple options. This paper reviews the main types of type 2 diabetes drugs on the market and describes the mechanism of action. The representative type 2 diabetes treatment drugs are listed, and the advantages and disadvantages of these representative drugs are preliminarily evaluated. This information is reviewed to help doctors with clinical medication.展开更多
AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile a...AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decr展开更多
In ovo feeding of vitamin C(VC)has positive effects on the growth performance,immune and antioxidant function in poultry,which indicates that increasing VC content in eggs may be of benefit.This study was to investiga...In ovo feeding of vitamin C(VC)has positive effects on the growth performance,immune and antioxidant function in poultry,which indicates that increasing VC content in eggs may be of benefit.This study was to investigate the effects of dietary VC supplementation on VC synthesis and transportation and egg deposition.In Exp.1,in order to select a suitable animal model,VC content was detected in different eggs from different layer species.Vitamin C content was lower in ISA Brown breeder eggs and Hy-Line Brown layer eggs(P<0.05)then in Arbor Acres breeder eggs.In Exp.2,a total of 24 Hy-Line Brown layers(42-week-old)were randomly divided into 3 treatments with 8 replicates and fed a basal diet with VC at 0,200 and 400 mg/kg.Sodium-dependent VC transporter 1 and 2(SVCT1 and SVCT2)expressions were higher in ileum than in duodenum and jejunum(P<0.05).SVCT1 expression was higher but SVCT2 expression was lower in the magnum than in the ovary(P<0.05).L-Gulonolactone oxidase(GLO)and SVCT7 expressions were higher but SVCT2 was lower in the kidney than in the liver(P<0.05).Dietary VC supplementation at 400 mg/kg increased SVCT1 expression in duodenum,ovary and magnum,but decreased GLO and SVCT1 expression in liver(P<0.05).Dietary VC supplementation at 200 and 400 mg/kg increased SVCT2 expression in duodenum,but decreased GLO and SVCT1 expression in kidney and SVCT2 expression in liver(P<0.05).Dietary VC supplementation promoted VC absorption in duodenum and jejunum,but reduced endogenous VC synthesis in liver and kidney.Although dietary VC supplementation enhanced VC transportation in ovary and magnum,it did not increase VC deposition in produced eggs.展开更多
Background:Many researches about in ovo feeding(IOF)of vitamin C(VC)are gradually carried out to explore physiological development in chicken,but little studies focus on VC synthesis capacity of the embryo itself,the ...Background:Many researches about in ovo feeding(IOF)of vitamin C(VC)are gradually carried out to explore physiological development in chicken,but little studies focus on VC synthesis capacity of the embryo itself,the selection of injection site and the effectiveness of IOF of VC.This study aims to explore the above problems.Results:Kidney and yolk sac were the main organs for VC synthesis and L-gulonolactone oxidase(GLO)expression was lower during pre-hatch development than that during post-hatch development.Sodium-dependent vitamin C transporter 1(SVCT1)expression was increased continuously in yolk sac from embryonic age 19(E19)to post-hatch day 1(D1)and in intestine(duodenum,jejunum and ileum)from E17 to D1.Plasma VC content was higher at D1 than that at D21 and D42.IOF of VC significantly reduced GLO expression in liver,kidney and yolk sac as well as SVCT1 expression in duodenum,jejunum and ileum,but increased the VC content in plasma,brain,kidney and liver.In addition,IOF of VC obviously reduced the embryonic morality and increased the hatchability under heat stress.Conclusions:This study suggested that IOF of VC at E11 in yolk was effective for embryonic VC supplementation.These findings provide a theoretical reference about the method of embryonic VC supplementation and effective methodology on embryonic VC nutrition in broiler chickens.展开更多
文摘BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure cont
文摘Heart failure(HF)is a major global health challenge,particularly among indi-viduals with type 2 diabetes mellitus(T2DM),who are at significantly higher risk of developing HF.Diabetic cardiomyopathy,a unique form of heart disease,often progresses silently until advanced stages.Recent research has focused on sodium-dependent glucose transporter 2 inhibitors(SGLT2i),originally developed for hyperglycemia,which have shown potential in reducing cardiovascular risks,including HF hospitalizations,irrespective of diabetic status.In this editorial we comment on the article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.The investigators examined the effects of SGLT2i on myocardial function in T2DM patients with asymptomatic HF,finding significant improvements in stroke volume index and reductions in systemic vascular resis-tance,suggesting enhanced cardiac output.Additionally,SGLT2i demonstrated anti-inflammatory and antioxidant effects,as well as blood pressure reduction,though the study’s limitations—such as small sample size and observational design—necessitate larger randomized trials to confirm these findings.The study underscores the potential of early intervention with SGLT2i in preventing HF progression in T2DM patients.
文摘We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.
文摘This article addresses the substantial findings of a study on sodium-dependent glucose transporter 2 inhibitors(SGLT2is)and their effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.The editorial explores the broader implications of the study findings for clinical practice,thus highlighting the pivotal role of SGLT2is in improving cardiac function,reducing oxidative stress,and attenuating inflammation.It emphasizes the importance of early intervention with SGLT2is in preventing the progression of diabetic cardio-myopathy;hence,these inhibitors have the potential to transform the manage-ment of asymptomatic heart failure in patients with diabetes.
文摘Type 2 Diabetes Mellitus (T2DM) is a systemic metabolic disorder with complex pathogenesis. In recent years, a variety of new T2DM drugs have emerged, such as sodium-dependent glucose transporters 2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. As traditional medicines, insulin also has developed kinds of formulations such as quick-acting or premixed insulin. In addition, new treatment schedules combining multiple drugs are also fully explored. The efficacy, the administration, the mechanism, the safety and the price of these drugs are all different, providing patients with multiple options. This paper reviews the main types of type 2 diabetes drugs on the market and describes the mechanism of action. The representative type 2 diabetes treatment drugs are listed, and the advantages and disadvantages of these representative drugs are preliminarily evaluated. This information is reviewed to help doctors with clinical medication.
文摘AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decr
基金funded by the National Key Research and Development Program of China(2017YFD0500500,20170502200)the National Natural Science Foundation of China(No.31972529)+1 种基金the Program for Shaanxi Science&Technology(2017TSCXLNY-04-04,2018ZDCXL-NY-0201,2018ZDXM-NY-051)the Program for Yangling Agricultural High-tech Industries Demonstration Zone(2018CXY-10)。
文摘In ovo feeding of vitamin C(VC)has positive effects on the growth performance,immune and antioxidant function in poultry,which indicates that increasing VC content in eggs may be of benefit.This study was to investigate the effects of dietary VC supplementation on VC synthesis and transportation and egg deposition.In Exp.1,in order to select a suitable animal model,VC content was detected in different eggs from different layer species.Vitamin C content was lower in ISA Brown breeder eggs and Hy-Line Brown layer eggs(P<0.05)then in Arbor Acres breeder eggs.In Exp.2,a total of 24 Hy-Line Brown layers(42-week-old)were randomly divided into 3 treatments with 8 replicates and fed a basal diet with VC at 0,200 and 400 mg/kg.Sodium-dependent VC transporter 1 and 2(SVCT1 and SVCT2)expressions were higher in ileum than in duodenum and jejunum(P<0.05).SVCT1 expression was higher but SVCT2 expression was lower in the magnum than in the ovary(P<0.05).L-Gulonolactone oxidase(GLO)and SVCT7 expressions were higher but SVCT2 was lower in the kidney than in the liver(P<0.05).Dietary VC supplementation at 400 mg/kg increased SVCT1 expression in duodenum,ovary and magnum,but decreased GLO and SVCT1 expression in liver(P<0.05).Dietary VC supplementation at 200 and 400 mg/kg increased SVCT2 expression in duodenum,but decreased GLO and SVCT1 expression in kidney and SVCT2 expression in liver(P<0.05).Dietary VC supplementation promoted VC absorption in duodenum and jejunum,but reduced endogenous VC synthesis in liver and kidney.Although dietary VC supplementation enhanced VC transportation in ovary and magnum,it did not increase VC deposition in produced eggs.
基金funded by the National Key Research and Development Program of China(2017YFD0500500,20170502200)the National Natural Science Foundation of China(No.31972529)+1 种基金the Innovative Transforming Project of Shaanxi Agricultural Achievements in Science&Technology(NYKJ-2018-YL15)the Program for Shaanxi Science&Technology from Shaanxi Provincial Science and Technology Department(2021TD-30).
文摘Background:Many researches about in ovo feeding(IOF)of vitamin C(VC)are gradually carried out to explore physiological development in chicken,but little studies focus on VC synthesis capacity of the embryo itself,the selection of injection site and the effectiveness of IOF of VC.This study aims to explore the above problems.Results:Kidney and yolk sac were the main organs for VC synthesis and L-gulonolactone oxidase(GLO)expression was lower during pre-hatch development than that during post-hatch development.Sodium-dependent vitamin C transporter 1(SVCT1)expression was increased continuously in yolk sac from embryonic age 19(E19)to post-hatch day 1(D1)and in intestine(duodenum,jejunum and ileum)from E17 to D1.Plasma VC content was higher at D1 than that at D21 and D42.IOF of VC significantly reduced GLO expression in liver,kidney and yolk sac as well as SVCT1 expression in duodenum,jejunum and ileum,but increased the VC content in plasma,brain,kidney and liver.In addition,IOF of VC obviously reduced the embryonic morality and increased the hatchability under heat stress.Conclusions:This study suggested that IOF of VC at E11 in yolk was effective for embryonic VC supplementation.These findings provide a theoretical reference about the method of embryonic VC supplementation and effective methodology on embryonic VC nutrition in broiler chickens.
