BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is ...BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.展开更多
BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL system...BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.展开更多
Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption,...Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.展开更多
目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于...目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。展开更多
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2020MH147National Natural Science Foundation of China,No.82002343.
文摘BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.
文摘BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.
基金Changshu Science and Technology Plan(Social Development)Project(No.CS202130)Key Project of Changshu No.2 People’s Hospital(No.CSEY2021007)。
文摘Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.
文摘目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。
