Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regard...Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.展开更多
Renal gluconeogenesis is one of the major pathways for endogenous glucose production.Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes.We reviewed pertinent studi...Renal gluconeogenesis is one of the major pathways for endogenous glucose production.Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes.We reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes.A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build up.Insulin-resistant models exhibit reduced insulin receptor(IR)expression and/or post-receptor signaling in their kidney tissue.Reduced IR expression or post-receptor signaling can cause impairment in insulin’s action on kidneys,which may increase renal gluconeogenesis in the state of insulin resistance.It is now established that the kidney contributes up to 20%of all glucose production via gluconeogenesis in the post-absorptive phase.However,the rate of renal glucose release excessively increases in diabetes.The rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose levels.Enhanced glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal gluconeogenesis.Overall,the available literature suggests that impairment in renal gluconeogenesis in an insulinresistant state may contribute to hyperglycemia in type 2 diabetes.展开更多
Fish oil (mainly omega 3 polyunsaturated fatty acids), differently from lard (mainly saturated fatty acids) has been suggested to have anti-inflammatory effects associated with amelioration of insulin sensibility. An ...Fish oil (mainly omega 3 polyunsaturated fatty acids), differently from lard (mainly saturated fatty acids) has been suggested to have anti-inflammatory effects associated with amelioration of insulin sensibility. An important role in skeletal muscle insulin resistance development has been recently attributed to mitochondrial dynamic behavior. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes and a shift toward fission process has been associated with skeletal muscle mitochondrial dysfunction and insulin resistance development. The present work aimed to evaluate if the replacement of lard with fish oil in high-fat diet positively affect skeletal muscle mitochondrial dynamic behavior in association with the improvement of insulin-resistance. Body weight gain, systemic insulin-resistance (glucose/insulin ratio), serum TNFα levels and skeletal muscle lipid content were assessed in rats fed a high-lard or high-fish-oil diet for 6 weeks. In skeletal muscle sections, immunohistochemical analysis were performed to detect the presence of insulin receptor substrate 1 (IRS1) and tyrosine phosphorylated IRS1 (key factor in insulin signalling pathway) as well as to detect the main proteins involved in mitochondrial fusion (MFN2 and OPA1) and fission (DRP1 and Fis1) processes. Skeletal muscle mitochondrial ultrastructural features were assessed by electron microscopy. High-fish oil feeding induced lower body weight gain, systemic inflammation and insulin-resistance development as well as skeletal muscle lipid accumulation compared to high-lard feeding. Skeletal muscle sections from high-fish oil fed rats exhibited a greater number of immunoreactive fibers for MFN2 and OPA1 proteins as well as weaker immunostaining for DRP1 and Fis1 compared to sections from high-lard fed rats. Electron microscopy observations suggested a prominent presence of fission events in L rats and fusion events in F rats. The positive effect of the replacement of lard with fish oil in high-fat diet on systemic and skeletal muscle insulin sensibility was associated to changes in mitochondrial dynamic behavior.展开更多
There are several causes of hepatocellular carcinoma(HCC), but certainly the hepatitis C virus(HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. De...There are several causes of hepatocellular carcinoma(HCC), but certainly the hepatitis C virus(HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. Determining early HCV clearance before an advanced liver disease develops, is absolutely necessary as this prevents the initiation of the cascade of events induced by HCV that may result in the development of HCC. The early treatment of the infection and the clearance of HCV represents today, in the age of the direct antiviral agents(DAAs), an extraordinary opportunity for true prevention of the development of HCV-related HCC.展开更多
This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus(T2 DM).Exposure to hypoxic conditions during exercise training positively c...This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus(T2 DM).Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects.Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions.Furthermore,post-exercise insulin sensitivity of T2 DM patients increases more when exercising under hypoxic than under normoxic conditions.Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions.Additionally,exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients.Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions.However,currently,evidence indicating that exposure to hypoxic conditions could positively affect T2 DM patients in the long-term is lacking.Therefore,further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body,considering different cycle lengths,duration of exposures,sessions per day,and the number of days,are necessary.In this review,we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits,which is potentially valuable in terms of clinical care as a new intervention for T2 DM patients.展开更多
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
基金The Indian Council of Medical Research,No.55/4/4/CARE-KD/2018/NCD-IIand the Council of Scientific&Industrial Research,No.09/590/(0159)/2016-EMR-1.
文摘Renal gluconeogenesis is one of the major pathways for endogenous glucose production.Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes.We reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes.A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build up.Insulin-resistant models exhibit reduced insulin receptor(IR)expression and/or post-receptor signaling in their kidney tissue.Reduced IR expression or post-receptor signaling can cause impairment in insulin’s action on kidneys,which may increase renal gluconeogenesis in the state of insulin resistance.It is now established that the kidney contributes up to 20%of all glucose production via gluconeogenesis in the post-absorptive phase.However,the rate of renal glucose release excessively increases in diabetes.The rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose levels.Enhanced glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal gluconeogenesis.Overall,the available literature suggests that impairment in renal gluconeogenesis in an insulinresistant state may contribute to hyperglycemia in type 2 diabetes.
文摘Fish oil (mainly omega 3 polyunsaturated fatty acids), differently from lard (mainly saturated fatty acids) has been suggested to have anti-inflammatory effects associated with amelioration of insulin sensibility. An important role in skeletal muscle insulin resistance development has been recently attributed to mitochondrial dynamic behavior. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes and a shift toward fission process has been associated with skeletal muscle mitochondrial dysfunction and insulin resistance development. The present work aimed to evaluate if the replacement of lard with fish oil in high-fat diet positively affect skeletal muscle mitochondrial dynamic behavior in association with the improvement of insulin-resistance. Body weight gain, systemic insulin-resistance (glucose/insulin ratio), serum TNFα levels and skeletal muscle lipid content were assessed in rats fed a high-lard or high-fish-oil diet for 6 weeks. In skeletal muscle sections, immunohistochemical analysis were performed to detect the presence of insulin receptor substrate 1 (IRS1) and tyrosine phosphorylated IRS1 (key factor in insulin signalling pathway) as well as to detect the main proteins involved in mitochondrial fusion (MFN2 and OPA1) and fission (DRP1 and Fis1) processes. Skeletal muscle mitochondrial ultrastructural features were assessed by electron microscopy. High-fish oil feeding induced lower body weight gain, systemic inflammation and insulin-resistance development as well as skeletal muscle lipid accumulation compared to high-lard feeding. Skeletal muscle sections from high-fish oil fed rats exhibited a greater number of immunoreactive fibers for MFN2 and OPA1 proteins as well as weaker immunostaining for DRP1 and Fis1 compared to sections from high-lard fed rats. Electron microscopy observations suggested a prominent presence of fission events in L rats and fusion events in F rats. The positive effect of the replacement of lard with fish oil in high-fat diet on systemic and skeletal muscle insulin sensibility was associated to changes in mitochondrial dynamic behavior.
文摘There are several causes of hepatocellular carcinoma(HCC), but certainly the hepatitis C virus(HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. Determining early HCV clearance before an advanced liver disease develops, is absolutely necessary as this prevents the initiation of the cascade of events induced by HCV that may result in the development of HCC. The early treatment of the infection and the clearance of HCV represents today, in the age of the direct antiviral agents(DAAs), an extraordinary opportunity for true prevention of the development of HCV-related HCC.
基金Supported by Ministry of Education of the Republic of Koreathe National Research Foundation of Korea,No. NRF-2019S1A5A2A03034583。
文摘This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus(T2 DM).Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects.Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions.Furthermore,post-exercise insulin sensitivity of T2 DM patients increases more when exercising under hypoxic than under normoxic conditions.Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions.Additionally,exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients.Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions.However,currently,evidence indicating that exposure to hypoxic conditions could positively affect T2 DM patients in the long-term is lacking.Therefore,further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body,considering different cycle lengths,duration of exposures,sessions per day,and the number of days,are necessary.In this review,we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits,which is potentially valuable in terms of clinical care as a new intervention for T2 DM patients.
