AIM：To confirm the role of angiopoietin-like protein 8（Angptl 8） in proliferative diabetic retinopathy（PDR）.METHODS：The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy（NDR） patients（...AIM：To confirm the role of angiopoietin-like protein 8（Angptl 8） in proliferative diabetic retinopathy（PDR）.METHODS：The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy（NDR） patients（idiopathic macular hole patients） were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay（ELISA）.Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type（WT） diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium（RPE） were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS：The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients（F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous）.After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity（P〈0.01）.In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay（1.486±0.042 vs 1.000±0.104,P〈0.05） and proliferating cell nuclear antigen（PCNA） expression（0.55±0.01 vs 0.29±0.03,P〈0.05）.The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1（4.973±0.205 vs 2.720±0.197,P〈0.05）,cyclin F（5.690±0.219 vs 4.297±0.292,P〈0.05） and E2 F2（2.297±0.102 vs 1.750±0.146,P〈0.05）,and reducing the expression of proliferation-inhibiting factors cdkn1（2.370±0.074 vs 3.317±0.135,P〈0.05） and cdkn2（4.793±0.065 vs 5.387±0.149,P〈0.05）.CONCLUSION：The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.展开更多
Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoi...Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.展开更多
目的研究冠状动脉粥样硬化性心脏病(coronary heart disease,CHD)患者血清骨形态发生蛋白4(bone morphogenetic protein 4,BMP-4),N1-甲基烟酰胺(N1-methylnicotinamide,me-Nam)和血管生成素样蛋白8(angiopoietinlike protein 8,ANGPTL8...目的研究冠状动脉粥样硬化性心脏病(coronary heart disease,CHD)患者血清骨形态发生蛋白4(bone morphogenetic protein 4,BMP-4),N1-甲基烟酰胺(N1-methylnicotinamide,me-Nam)和血管生成素样蛋白8(angiopoietinlike protein 8,ANGPTL8)水平检测的临床意义。方法选取2018年1月~2020年1月佛山市中医院诊治的86例CHD患者作为CHD组,以健康体检的60例健康人群为对照组,检测CHD组及对照组血清BMP-4,me-Nam,ANGPTL8,血脂及炎症因子水平。比较不同冠状动脉狭窄程度、不同病变支数患者血清BMP-4,me-Nam及ANGPTL8水平。Pearson线性相关分析CHD组患者血清BMP-4,me-Nam和ANGPTL8之间的相关性及三者与Gensini积分、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和超敏C反应蛋白(hs-CRP)的相关性。ROC曲线分析血清BMP-4,me-Nam,ANGPTL8及联合检测对CHD组患者的诊断价值。结果与对照组相比,CHD组患者高血压史、糖尿病史占比较高,TC,TG,LDL-C,IL-6,TNF-α及hs-CRP水平明显增高,HDL-C水平明显降低,差异均有统计学意义(t=5.950~28.084,均P<0.05)。与对照组相比,CHD组患者血清BMP-4,me-Nam,ANGPTL8水平明显增高,差异均有统计学意义(t=14.201,13.495,37.538,均P<0.05)。随着Gensini积分升高或病变支数的增加,CHD患者的血清BMP-4,me-Nam,ANGPTL8有逐渐升高的趋势(χ^(2)=80.976,75.688,108.641,均P<0.05)。CHD患者血清BMP-4表达与me-Nam,ANGPTL8表达呈显著正相关(r=0.567,0.610,均P<0.05),me-Nam与ANGPTL8的表达呈显著正相关(r=0.562,P=0.000)。血清BMP-4,me-Nam,ANGPTL8及联合检测的曲线下面积分别为0.707(95%CI:0.601~0.812),0.713(95%CI:0.612~0.833),0.759(95%CI:0.667~0.850)及0.847(95%CI:0.722~0.908),联合诊断的诊断效能大于任一单一指标的诊断效能。结论CHD患者血清BMP-4,me-Nam及ANGPTL8水平升高,三者与血脂、炎症因子、冠状动脉狭窄程度及病变支数有关,检测其水平可为CHD病情评估提供一定参考。展开更多
血管生成素样蛋白8(angiopoietin-like protein 8,ANGPTL8)是最新发现的ANGPTLs家族成员,是一种与脂类代谢相关的分泌性蛋白因子。作者综述了ANGPTL8基因的结构、定位、表达调控、功能等方面的研究进展,对该基因作为治疗脂类相关疾病的...血管生成素样蛋白8(angiopoietin-like protein 8,ANGPTL8)是最新发现的ANGPTLs家族成员,是一种与脂类代谢相关的分泌性蛋白因子。作者综述了ANGPTL8基因的结构、定位、表达调控、功能等方面的研究进展,对该基因作为治疗脂类相关疾病的靶基因的前景做了展望。展开更多
文摘AIM：To confirm the role of angiopoietin-like protein 8（Angptl 8） in proliferative diabetic retinopathy（PDR）.METHODS：The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy（NDR） patients（idiopathic macular hole patients） were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay（ELISA）.Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type（WT） diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium（RPE） were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS：The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients（F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous）.After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity（P〈0.01）.In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay（1.486±0.042 vs 1.000±0.104,P〈0.05） and proliferating cell nuclear antigen（PCNA） expression（0.55±0.01 vs 0.29±0.03,P〈0.05）.The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1（4.973±0.205 vs 2.720±0.197,P〈0.05）,cyclin F（5.690±0.219 vs 4.297±0.292,P〈0.05） and E2 F2（2.297±0.102 vs 1.750±0.146,P〈0.05）,and reducing the expression of proliferation-inhibiting factors cdkn1（2.370±0.074 vs 3.317±0.135,P〈0.05） and cdkn2（4.793±0.065 vs 5.387±0.149,P〈0.05）.CONCLUSION：The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.
文摘Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.
文摘目的研究冠状动脉粥样硬化性心脏病(coronary heart disease,CHD)患者血清骨形态发生蛋白4(bone morphogenetic protein 4,BMP-4),N1-甲基烟酰胺(N1-methylnicotinamide,me-Nam)和血管生成素样蛋白8(angiopoietinlike protein 8,ANGPTL8)水平检测的临床意义。方法选取2018年1月~2020年1月佛山市中医院诊治的86例CHD患者作为CHD组,以健康体检的60例健康人群为对照组,检测CHD组及对照组血清BMP-4,me-Nam,ANGPTL8,血脂及炎症因子水平。比较不同冠状动脉狭窄程度、不同病变支数患者血清BMP-4,me-Nam及ANGPTL8水平。Pearson线性相关分析CHD组患者血清BMP-4,me-Nam和ANGPTL8之间的相关性及三者与Gensini积分、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和超敏C反应蛋白(hs-CRP)的相关性。ROC曲线分析血清BMP-4,me-Nam,ANGPTL8及联合检测对CHD组患者的诊断价值。结果与对照组相比,CHD组患者高血压史、糖尿病史占比较高,TC,TG,LDL-C,IL-6,TNF-α及hs-CRP水平明显增高,HDL-C水平明显降低,差异均有统计学意义(t=5.950~28.084,均P<0.05)。与对照组相比,CHD组患者血清BMP-4,me-Nam,ANGPTL8水平明显增高,差异均有统计学意义(t=14.201,13.495,37.538,均P<0.05)。随着Gensini积分升高或病变支数的增加,CHD患者的血清BMP-4,me-Nam,ANGPTL8有逐渐升高的趋势(χ^(2)=80.976,75.688,108.641,均P<0.05)。CHD患者血清BMP-4表达与me-Nam,ANGPTL8表达呈显著正相关(r=0.567,0.610,均P<0.05),me-Nam与ANGPTL8的表达呈显著正相关(r=0.562,P=0.000)。血清BMP-4,me-Nam,ANGPTL8及联合检测的曲线下面积分别为0.707(95%CI:0.601~0.812),0.713(95%CI:0.612~0.833),0.759(95%CI:0.667~0.850)及0.847(95%CI:0.722~0.908),联合诊断的诊断效能大于任一单一指标的诊断效能。结论CHD患者血清BMP-4,me-Nam及ANGPTL8水平升高,三者与血脂、炎症因子、冠状动脉狭窄程度及病变支数有关,检测其水平可为CHD病情评估提供一定参考。
