目的对叶酸、维生素B_(12)(VB_(12))、二甲双胍联用对2型糖尿病(T2DM)患者的治疗作用。方法选取2021年2月至2023年3月浙江省医疗健康集团长兴医院收治的112例T2DM患者,采用随机数字表法分为对照组(VB_(12)^(+)二甲双胍,56例)和研究组(叶...目的对叶酸、维生素B_(12)(VB_(12))、二甲双胍联用对2型糖尿病(T2DM)患者的治疗作用。方法选取2021年2月至2023年3月浙江省医疗健康集团长兴医院收治的112例T2DM患者,采用随机数字表法分为对照组(VB_(12)^(+)二甲双胍,56例)和研究组(叶酸^(+)VB_(12)^(+)二甲双胍,56例)。对比血糖、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)水平、胰岛素抵抗指数(HOMA-IR)和同型半胱氨酸(Hcy)水平、临床疗效、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平、Th1、Th17、Th1/Th17水平,不良反应及并发症。结果治疗后,研究组空腹血糖(FPG)、餐后2 h血糖(2 h PG)、HOMA-IR、HbA1c、FINS和Hcy均低于治疗前与对照组(P<0.05);研究组总有效率更高(P<0.05);治疗后研究组CD4^(+)、CD4^(+)/CD8^(+)均高于治疗前和对照组(P<0.05),CD8^(+)低于治疗前和对照组(P<0.05);治疗后,研究组Th1、Th17水平低于治疗前和对照组(P<0.05),Th1/Th17高于治疗前和对照组(P<0.05);2组患者不良反应发生率比较差异无统计学意义(P>0.05);研究组并发症发生率低于对照组(P<0.05)。结论叶酸与VB_(12)、二甲双胍联用治疗T2DM有助于控糖,还可提高免疫,调节Th1/Th17平衡,且安全可靠,有助于减少并发症。展开更多
6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring...6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring glucose consuming ability in dexamethasone(DXM)-induced insulin resistant 3T3-L1 adipocytes.Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion.Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor c and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis,and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85,Akt2 and AS160,thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.展开更多
Insulin resistance(IR)is associated with several metabolic disorders,including type 2 diabetes(T2D).The development of IR in insulin target tissues involves genetic and acquired factors.Persons at genetic risk for T2D...Insulin resistance(IR)is associated with several metabolic disorders,including type 2 diabetes(T2D).The development of IR in insulin target tissues involves genetic and acquired factors.Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance.Several rodent models for both IR and T2D are being used to study the disease pathogenesis;however,these models cannot recapitulate all the aspects of this complex disorder as seen in each individual.Human pluripotent stem cells(hPSCs)can overcome the hurdles faced with the classical mouse models for studying IR.Human induced pluripotent stem cells(hiPSCs)can be generated from the somatic cells of the patients without the need to destroy a human embryo.Therefore,patient-specific hiPSCs can generate cells genetically identical to IR individuals,which can help in distinguishing between genetic and acquired defects in insulin sensitivity.Combining the technologies of genome editing and hiPSCs may provide important information about the genetic factors underlying the development of different forms of IR.Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.In this review,we summarize the factors involved in the development of IR in the insulin-target tissues leading to diabetes.Also,we highlight the use of hPSCs to understand the mechanisms underlying the development of IR.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worl...Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.展开更多
文摘目的对叶酸、维生素B_(12)(VB_(12))、二甲双胍联用对2型糖尿病(T2DM)患者的治疗作用。方法选取2021年2月至2023年3月浙江省医疗健康集团长兴医院收治的112例T2DM患者,采用随机数字表法分为对照组(VB_(12)^(+)二甲双胍,56例)和研究组(叶酸^(+)VB_(12)^(+)二甲双胍,56例)。对比血糖、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)水平、胰岛素抵抗指数(HOMA-IR)和同型半胱氨酸(Hcy)水平、临床疗效、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平、Th1、Th17、Th1/Th17水平,不良反应及并发症。结果治疗后,研究组空腹血糖(FPG)、餐后2 h血糖(2 h PG)、HOMA-IR、HbA1c、FINS和Hcy均低于治疗前与对照组(P<0.05);研究组总有效率更高(P<0.05);治疗后研究组CD4^(+)、CD4^(+)/CD8^(+)均高于治疗前和对照组(P<0.05),CD8^(+)低于治疗前和对照组(P<0.05);治疗后,研究组Th1、Th17水平低于治疗前和对照组(P<0.05),Th1/Th17高于治疗前和对照组(P<0.05);2组患者不良反应发生率比较差异无统计学意义(P>0.05);研究组并发症发生率低于对照组(P<0.05)。结论叶酸与VB_(12)、二甲双胍联用治疗T2DM有助于控糖,还可提高免疫,调节Th1/Th17平衡,且安全可靠,有助于减少并发症。
基金China National Major Projects of Science&Technology(2014ZX100050022009ZX09103-436)+1 种基金the Young Academic Leader Raising Foundation of Yunnan Province(No.2009CI073)the foundation from Chinese Academy of Sciences to Gang Xu,and the Program for Research Team in South China Chinese Medicine Collaborative Innovation Center of Guangdong,China(A1-AFD01514A07).
文摘6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring glucose consuming ability in dexamethasone(DXM)-induced insulin resistant 3T3-L1 adipocytes.Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion.Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor c and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis,and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85,Akt2 and AS160,thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.
基金the Qatar National Research Fund,No.NPRP10-1221-160041.
文摘Insulin resistance(IR)is associated with several metabolic disorders,including type 2 diabetes(T2D).The development of IR in insulin target tissues involves genetic and acquired factors.Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance.Several rodent models for both IR and T2D are being used to study the disease pathogenesis;however,these models cannot recapitulate all the aspects of this complex disorder as seen in each individual.Human pluripotent stem cells(hPSCs)can overcome the hurdles faced with the classical mouse models for studying IR.Human induced pluripotent stem cells(hiPSCs)can be generated from the somatic cells of the patients without the need to destroy a human embryo.Therefore,patient-specific hiPSCs can generate cells genetically identical to IR individuals,which can help in distinguishing between genetic and acquired defects in insulin sensitivity.Combining the technologies of genome editing and hiPSCs may provide important information about the genetic factors underlying the development of different forms of IR.Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.In this review,we summarize the factors involved in the development of IR in the insulin-target tissues leading to diabetes.Also,we highlight the use of hPSCs to understand the mechanisms underlying the development of IR.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
文摘Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.
