2型糖尿病内脏脂肪含量与胰岛β细胞功能及胰岛素抵抗的关系研究

目的:研究2型糖尿病患者内脏脂肪含量与胰岛β细胞功能及胰岛素抵抗的关系。方法:对65例初诊2型糖尿病患者采用256 CT平脐经L4、5水平进行扫描并测量皮下及内脏脂肪含量,并以BMI不同进行分组,即体重正常组、超重组、肥胖组。采用稳态模式评估法(HOMA)计算胰岛素抵抗指数、胰岛B细胞分泌功能,测量入组患者的相关人体指标、空腹血生化检查指标。结果:超体重组、肥胖组患者腰围、体重指数(body mass index, BMI)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、空腹血糖,(fasting blood-glucose, FBG)、空腹胰岛素(fasting insulin, FINS)INS、稳态模型胰岛素抵抗指数(Homeostatic Model Assessment for Insulin Resistance, HOMA-IR)、胰岛β细胞功能指数(Homeostasis model assessment-β,HOMA-β)指标肥胖组、超重组均明显高于正常体重组(P0.05),超体重组、肥胖组内脏脂肪含量、内脏脂肪面积、皮下脂肪含量、脂肪总含量、脂肪百分比,超重组、肥胖组均明显高于正常体重组(P0.05),且肥胖组各项指标明显高于超重组(P0.05)。多元回归分析显示腹部脂肪总含量、内脏脂肪含量、皮下脂肪含量、内脏脂肪面积、BMI与胰岛素抵抗呈正相关,而其中内脏脂肪含量及面积关系最密切。结论:内脏脂肪含量是2型糖尿病胰岛素抵抗及B细胞功能变化的独立影响因素。     

不同强度有氧跑有助于改善IGR老年人的症状

为了探讨不同强度持续跑步干预对糖调节受损(impaired glucose regulation,IGR)人群胰岛素敏感性、骨密度、糖调节、激素分泌的影响效果差异,为研发促进IGR人群糖调节能力恢复的运动处方提供实证参考,本研究选定90名糖调节受损老年人为本研究实验对象,进行随机分组,随机分为Fatmax强度跑步组(F组,n=30);AT强度跑步组(A组,n=30);对照组(C组,n=30)。在干预开始前1周内对受试者进行前测(BMD,骨代谢,FPG,OGTT-2h,HOMA-IR,IGF-1,生长激素分泌指标)。干预前3天,F组进行FATMAX强度测试、A组进行AT强度测试,各组按照运动计划进行为期24周的干预,运动干预结束后测。通过24周干预,F组和A组受试者的BMI、体脂率后测结果显著低于前测结果(p<0.05),而C组BMI和体脂率前后测结果对比没有显著性差异(p>0.05);F组、A组的FPG和OGTT-2h后测结果显著低于前测,且显著低于C组后测结果(p<0.05);F组和A组受试者的血清GH、IGF-1以及BGP的后测结果明显高于其前测结果和C组后测结果(p<0.05),而C组GH、IGF-1和BGP前后测结果对比没有显著性差异(p>0.05)。F组和A组受试者股骨颈BMD、大转子骨BMD、Ward’s三角区BMD后测结果显著高于前测结果和C组后测结果(p<0.05)。IGR老年人长期进行以Fatmax和AT强度进行长时间有氧跑步,不仅能够增加其下肢骨密度、促进骨生产和改善骨代谢,而且降低FPG、缓解胰岛素抵抗、促进GH、IGF-1分泌。其机制可能是IGR老年人长期进行中低强度有氧跑会提升血清GH、IGF-1浓度,而GH和IGF-1能够促进胰岛素的分泌合成以及促进成骨细胞工作,从而缓解IGR老年人的胰岛素抵抗和增加下肢BMD。     

Insulin mimetic lanostane triterpenes from the cultivated mushroom Ganoderma orbiforme

Two new lanostane triterpenes, ganorbifoins A and B (1-2), together with the known compound (25S,3′S)-(+)-12α-hydroxy-3α-(3′-hydroxy-4′-methoxycarbonyl-3′-methylbutiryloxy)-24-methyllanosta-824-(31)-dien-26-oic acid (3) were isolated from the cultivated fruiting bodies of Ganoderma orbiforme. The structures of isolates were determined by extensive analysis of NMR and HRESIMS. All compounds induced glucose uptake in zebrafish-based system at the concentration of 10 μM. And the best performing compound is ganorbifoin A. Compounds 2 and 3 exhibited an inhibitory effect on nitric oxide production in LPS-induced BV-2 microglia cells at the concentration of 20 μM.     

CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.     

智能胰岛素递送系统用于糖尿病治疗的研究进展

糖尿病是继癌症和心血管疾病之后危害人类健康的第三大疾病。1型糖尿病或2型糖尿病治疗需要每日注射或持续输注外源性胰岛素,以调节体内血糖达到正常水平。然而目前胰岛素的治疗手段受到低血糖风险的限制。以生物材料为载体构建递送系统可提高胰岛素的生物利用度,减少不良反应的发生。因此,基于智能胰岛素递送系统的研究开发对提高胰岛素给药的可控性是必要的。对近年来胰岛素的不同给药方法进行综述,阐述智能胰岛素递送系统的作用机制,并探讨不同给药方法下智能胰岛素递送系统的研究现状及存在的问题。     

多囊卵巢综合征肥胖患者血清维生素D、铁蛋白水平、sICAM-1与胰岛素抵抗、糖脂代谢指标的相关性

摘要 目的：探讨多囊卵巢综合征（PCOS）肥胖患者血清维生素D、铁蛋白、可溶性细胞间粘附分子-1（sICAM-1）水平与胰岛素抵抗、糖脂代谢指标的相关性。方法：2018年8月到2021年11月,选择在本院妇科诊治的PCOS患者65例作为研究对象,分为PCOS肥胖组（n=30,体重指数＜28 kg/m²）和PCOS非肥胖组（n=35,体重指数<28 kg/m²）。检测与计算两组清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标并进行相关性分析。结果：两组的血清甲状腺素（T4）、促甲状腺激素（TSH）与泌乳素（PRL）对比差异无统计学意义（P>0.05）,肥胖组的血清促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）水平高于非肥胖组（P<0.05）。肥胖组的血清铁蛋白、sICAM-1水平高于非肥胖组,血清维生素D水平低于非肥胖组（P<0.05）。肥胖组的胰岛素抵抗指数（HOMA-IR）、胰岛素水平（FINS）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）较非肥胖组,高密度脂蛋白胆固醇（HDL-C）低于非肥胖组（P<0.05）。在PCOS肥胖患者中,Pearson分析显示血清维生素D、铁蛋白、sICAM-1与胰岛素抵抗、糖脂代谢指标都存在相关性（P<0.05）。结论：PCOS肥胖患者与非肥胖患者的血清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标水平存在差异,血清维生素D、铁蛋白、sICAM-1水平与胰岛素抵抗、糖脂代谢指标存在相关性。     

军事飞行人员非酒精性脂肪肝病患者白细胞计数、C反应蛋白、尿酸与糖脂代谢、胰岛素抵抗和肝纤维化指标的相关性研究

摘要 目的：研究军事飞行人员非酒精性脂肪肝病（NAFLD）患者白细胞计数（WBC）、C反应蛋白（CRP）、尿酸（UA）与糖脂代谢、胰岛素抵抗和肝纤维化指标的相关性。方法：选择2018年7月至2021年12月期间海军青岛特勤疗养中心收治的100例NAFLD军事飞行人员作为NAFLD组,另取同期健康体检者90例作为对照组。检测并对比两组的WBC、CRP、UA、糖脂代谢、胰岛素抵抗以及肝纤维化相关指标,采用Pearson相关系数分析WBC、CRP、UA与糖脂代谢、胰岛素抵抗和肝纤维化指标的相关性。结果：NAFLD组的WBC、CRP、UA水平均明显高于对照组（P<0.05）。NAFLD组的空腹血糖（FBG）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、空腹胰岛素（FINS）、稳态模型胰岛素抵抗指数（HOMA-IR）水平均高于对照组,高密度脂蛋白胆固醇（HDL-C）水平低于对照组（P<0.05）。NAFLD组的Ⅲ型前胶原肽（PC-Ⅲ）、层粘连蛋白（LN）、透明质酸（HA）、Ⅳ型胶原（Col-Ⅳ）水平均明显高于对照组（P<0.05）。Pearson相关性分析结果显示, WBC、CRP、UA与TC、TG、LDL-C、HOMA-IR、PC-Ⅲ、LN、HA、Col-Ⅳ均呈正相关,而与HDL-C呈负相关（P<0.05）; WBC、CRP、UA与FBG、FINS无显著相关性（P>0.05）。结论：军事飞行人员NAFLD患者体内WBC、CRP、UA明显升高,且与糖脂代谢紊乱、胰岛素抵抗和肝纤维化有关。     

Proteomics and PUGNAcity will overcome questioning of insulin resistance induction by nonselective inhibition of O‐GlcNAcase

PTMs are the ultimate elements that perfect the existence and the activity of proteins. Owing to PTM, not less than 500 millions biological activities arise from approximately 20 000 protein‐coding genes in human. Hundreds of PTM were characterized in living beings among which is a large variety of glycosylations. Many compounds have been developed to tentatively block each kind of glycosylation so as to study their biological functions but due to their complexity, many off‐target effects were reported. Insulin resistance exemplifies this problem. Several independent groups described that inhibiting the removal of O‐GlcNAc moieties using O‐(2‐acetamido‐2‐deoxy‐d‐glucopyranosylidene)amino‐N‐phenylcarbamate (PUGNAc), a nonselective inhibitor of the nuclear and cytoplasmic O‐GlcNAcase, induced insulin resistance both in vivo and ex vivo. The development of potent and highly selective O‐GlcNAcase inhibitors called into question that elevated O‐GlcNAcylation levels are responsible for insulin resistance; these compounds not recapitulating the insulin‐desensitizing effect of PUGNAc. To tackle this intriguing problem, a South Korean group recently combined ATP‐affinity chromatography and gel‐assisted digestion to identify proteins, differentially expressed upon treatment of 3T3‐L1 adipocytes with PUGNAc, involved in protein turnover and insulin signaling.     

不同胰岛素给药方式救治糖尿病酮症酸中毒临床研究

目的：比较不同胰岛素给药方式治疗糖尿病酮症酸中毒（DKA）的临床疗效。方法：82例DKA患者随机分为胰岛素泵持续皮下输液胰岛素（CSⅡ）组和微量泵持续静脉泵入胰岛素（CXqI）组各41例,分别给予胰岛素泵持续皮下输注胰岛素和小剂量胰岛素持续微量泵静脉泵入不同胰岛素给药方式,观察两组治疗后血糖变化、血糖达标时间、尿酮体变化、pH值变化、胰岛素平均日用量、平均低血糖次数及平均住院时间。结果：两组治疗后空腹血糖、餐后血糖显著下降及血糖达标时间显著缩短差异无统计学意义（P〉0．05）;CSII组尿酮体转阴时间（22．3±7．4）h短于CVII组（32．1±12．1）h（P〈0．01）;CSII组PH值恢复时间（9．4±2．5）h短于CVII组（15．7±3．5）h（P〈0．01）;CSII组平均胰岛素日用量为（47±5）U比CVII组（58＋7）U少（P〈0．01）;CSII组人均低血糖次数为（0．6±O．5）次／人。少于CVII组（1．5±0．8）次／人（P〈O．01）;CSII组住院时间（9．8±1．2）天明显比CVII组（12．5±2．0）天短（P〈0．01）。结论：CSII相较于CVII能更快更有效的纠正代谢紊乱,减少胰岛素日用量,缩短住院时间,从而提高临床疗效。具有较高的安全性及患者依从性。