Persistently High Glycated Hemoglobin in a Subgroup of Type 2 Diabetic Patients Who Failed Usual Oral Antihyperglycemics and Insulin in Côte d’Ivoire

Background: Type II diabetes mellitus is associated with multiple metabolic derangements which can cause secondary pathophysiological changes in multiple organ systems. This in turn can impose a heavy burden of morbidity and mortality from micro‑ and macro‑vascular complications. This study aimed to describe the metabolic and therapeutic profile of a subgroup of type 2 diabetic patients who have treatment failure with oral anti-hyperglycemic agents with persistent hyperglycemia despite insulin treatment. Methods: 60 type 2 diabetic patients in treatment failure with oral antidiabetics and under insulin treatment, aged 35 to 70 years, were recruited at the Diabetes Clinic of the University Teaching Hospital of Treichville in Abidjan, Côte d’Ivoire. Blood samples were collected in tubes containing Ethylenediaminetetraacetic Acid (EDTA) to determine glycated hemoglobin (HbA1c). Results: The average age of the population was 54 ± 9.38 years with a sex ratio (M/F) of 0.3, an average BMI of 30.25 ± 5 kg/m2, and an average HbA1c of 10.1% ± 1.6% for an average diabetes duration of 11.8 ± 5.8 years. The average insulin dose was 74.556 ± 16.21 UI/day, and the average duration of insulin treatment was 5.4 ± 3.1 years. The average HbA1c value was 10.1% ± 1.87% in men against 10.03% ± 1.53% in women with no significant difference (p = 0.1). The mean HbA1c values according to patient weight were 10.08% ± 2.05% for normal weight, 9.55% ± 2.26% for overweight, and 10.57% for obese, with no significant difference between the three groups of patients (p = 0.1). Conclusion: This study showed a persistence increase in glycated hemoglobin regardless of the treatment regimen, duration, and dose of insulin treatment in the subpopulation of type 2 diabetic patients.

Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in Ovariectomized Rats

Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized （OVX） control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to high fat diet and water for 9 weeks. No significant difference was found in body weight （BW）, total abdominal fat, food intake and food utilization rate between OVX control group and 20VX groups. However, the fasting blood glucose and blood lipid levels were significantly higher in 20VX groups than in OVX control group （P〈0.05）. Intraperitoneal glucose tolerance test （IGTI＂） showed that the area under AUC was smaller in 20VX groups than in OVX control group （P〈0.05）. These findings showed that soy isoflavone crude extract supplementation can improve glucose tolerance and prevent high fat diet-induced insulin resistance in ovariectomized rats.

Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats

AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.

Characterization of inflammation and insulin resistance in high-fat diet-induced male C57BL/6J mouse model of obesity

Background: Animal models of diet-induced obesity(DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be considered when designing new experiments. Here, we investigated the effect of 9 weeks high-fat diet(HFD) intervention, providing 60% energy from fat, on parameters of inflammation and insulin resistance in male C57 BL/6 J mice.Methods: Six weeks old mice were initiated on regular diet(RD) or HFD providing 60 kcal energy from fat for 9 weeks. Fasting blood glucose levels were measured by glucometer, and fasting plasma levels of insulin and proinflammatory cytokines by Luminex assay. Insulin sensitivity was evaluated by using QUICKI and HOMA2 indexes.Results: HFD mice showed ~ 40% higher body weight and ~ 20% larger abdominal circumference, due to an increase in the white adipose tissue mass. Liver examination revealed increased size and higher hepatic lipid accumulation in livers from HFD mice compared to their RD counterparts. Animals from the HFD group were characterized with significantly higher presence of crown-like structures(CLS) in WAT and higher plasma levels of proinflammatory cytokines(TNF-α, IL-6, leptin, MCP-1, PAI-1, and resistin). HFD-fed mice also demonstrated impaired insulin sensitivity(lower QUICKI, higher HOMA-insulin resistance(HOMA-IR), and lower HOMA-percent sensitivity(HOMA-%S)) index values.Conclusion: Male C57 BL/6 J mice on 9 weeks HFD providing 60 kcal energy from fat display impaired insulin sensitivity and chronic inflammation, thus making this DIO mouse model appropriate for studies of early stages of obesity-related pathology.

High-Lard and High-Fish Oil Diets Differ in Their Effects on Insulin Resistance Development, Mitochondrial Morphology and Dynamic Behaviour in Rat Skeletal Muscle

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.

腹腔镜术前口服高糖溶液对结直肠癌患者的影响

目的探讨结直肠癌患者腹腔镜术前口服高糖溶液对术后胃肠功能、炎症水平及胰岛素抵抗的影响。方法选择2020年5月至2022年7月南京中医药大学附属连云港市中医院收治的78例结直肠癌患者为研究对象,利用随机数字表法将其分为两组,观察组39例,对照组39例。观察组男20例、女19例,年龄38~75(56.65±8.43)岁,Dukes分期:Ⅰ期21例,Ⅱ期18例;对照组男19例、女20例,年龄39~74(55.79±8.39)岁,Dukes分期:Ⅰ期22例,Ⅱ期17例。对照组采用常规治疗,观察组术前采用高糖溶液口服。比较两组患者的术后胃肠功能、炎症水平、胰岛素抵抗指数及并发症情况。采用独立样本t检验、配对t检验和χ^(2)检验。结果治疗后,观察组术后肛门排气时间、术后首次排便时间、住院时间分别为(23.97±2.85)h、(14.35±5.43)h、(5.69±0.87)d,均短于对照组(34.68±3.94)h、(21.06±7.47)h、(9.52±1.14)d,差异均有统计学意义(均P<0.05);治疗后,观察组患者肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)水平分别是(141.85±30.29)ng/L、(8.69±2.05)mg/L、(7.34±0.93)ng/L,均低于对照组(182.46±33.37)ng/L、(15.33±2.78)mg/L、(9.97±1.54)ng/L,差异均有统计学意义(均P<0.05);治疗后,观察组胰岛素抵抗指数(5.14±0.31),低于对照组(7.75±0.96),差异有统计学意义(P<0.05);治疗后,观察组并发症总发生率为10.25%(4/39),低于对照组的28.21%(11/39),差异有统计学意义(P<0.05)。结论腹腔镜术前口服高糖溶液能有效改善结直肠癌患者术后的胃肠功能,降低患者炎症水平,改善患者胰岛素抵抗,降低并发症发生率,值得推广。

RNA m^(6)A甲基化修饰在脂肪细胞胰岛素抵抗中的作用机制

目的:探讨RNA m^(6)A甲基化修饰在脂肪细胞胰岛素抵抗中的作用及机制。方法:收集2型糖尿病患者术中赘余皮下脂肪组织,以非2型糖尿病患者同样组织为对照,检测组间RNA m^(6)A水平。高脂饮食诱导C57BL/6J小鼠构建胰岛素抵抗(in⁃sulin resistance,IR)模型(HFD组,n=5,60%高脂饲料喂养16周),对照组10%低脂饲料喂养16周(CD组,n=5)。模型构建成功后,取附睾周围脂肪组织行表观转录组学m^(6)A甲基化修饰芯片检测,并借助MeRIP-qPCR实验、RT-qPCR以及RNA结合蛋白免疫沉淀测定(RNA Binding Protein Immunoprecipitation Assay,RIP)实验验证胰岛素信号转导相关基因变化;进一步观察METTL3小分子抑制剂STM2457对高脂饮食诱导下小鼠胰岛素信号转导基因的影响。结果:2型糖尿病患者和小鼠IR模型脂肪组织中总体m^(6)A修饰水平均升高(患者200 ng RNA t=-8.375,P<0.001;患者100 ng RNA t=-3.722,P=0.006;患者50 ng RNA t=-4.937;P=0.001;小鼠100 ng RNA t=-3.590,P=0.023;小鼠50 ng RNA t=-2.760,P=0.025)。表观转录组学检测证实IR的脂肪组织中1175个基因发生高m^(6)A修饰,55个基因发生低m^(6)A修饰,同时有182个基因呈现高m^(6)A修饰且低表达,包括AKT2、INSR、PIK3R1、ACACA、SREBF1等5个胰岛素信号转导关键基因,其中AKT2、INSR、ACACA、SREBF1等4个基因被确证并证实其与METTL3存在直接结合,其m^(6)A修饰水平受METTL3正向调控。STM2457作用下,胰岛素敏感性提高,且AKT2、INSR、ACACA、SREBF1转录水平上调,提示IR表型改善明显。结论:高脂饮食通过METTL3诱导脂肪细胞胰岛素信号转导基因AKT2、INSR、ACACA、SREBF1发生m^(6)A高甲基化修饰,诱导其低表达,阻滞胰岛素信号转导,进而参与诱发IR。

原发性脑出血血肿远隔部位DWI高信号病灶与胰岛素抵抗相关性研究

目的探讨原发性脑出血患者弥散加权成像出现高信号病灶的危险因素。方法回顾性分析2021年1月至2022年9月九江市第一人民医院收治的病程2周内的132例原发性脑出血患者的临床资料。根据是否发生血肿远隔部位高信号病灶(R-DWILs)将其分为A组(发生R-DWILs)以及B组(未发生R-DWILs)。比较两组患者人口学特征指标、血液学指标水平。采用多因素logistic回归分析明确原发性脑出血R-DWILs的影响因素。结果A组患者的年龄高于B组,差异有统计学意义(P<0.05)。两组患者的性别、糖尿病、高血压、心房颤动、吸烟、饮酒、发病至入院时间、血肿体积比较,差异无统计学意义(P>0.05)。A组患者的空腹血糖(FPG)、胰岛素抵抗指数(HOMA-IR)、中性粒细胞与淋巴细胞计数比值(NLR)高于B组,差异有统计学意义(P<0.05)。两组患者的白细胞计数、红细胞沉降率比较,差异无统计学意义(P>0.05)。多因素logistic回归分析显示,高龄、高FPG、高HOMA-IR以及高NLR均是原发性脑出血R-DWILs的独立危险因素(OR=1.492、2.173、1.686、1.736,95%CI:1.045~1.896、1.356~3.682、1.145~4.371、1.166~3.501,P=0.001、<0.001、<0.001、<0.001)。结论胰岛素抵抗增加了原发性脑出血患者R-DWILs发生的风险。

母鼠高脂饮食与运动干预对雄性子代胰岛素敏感性及下丘脑弓状核的影响

背景:肥胖母体的子代,有些代谢基因在某些环境影响下处于“沉默”状态,这些“沉默”的基因可能因后天环境的影响又被“唤醒”,继而引起代谢调控紊乱。目的:雄性子代在不同饮食结构的情况下,探索母鼠长期高脂和运动干预的代谢遗传效应。方法:3周龄雌性C57BL/6小鼠70只,随机分成高脂安静组与高脂运动组,干预16周后自然分娩。2组在4周哺乳期结束后,各随机抽取子代雄性小鼠16只,共32只分为4组:高脂安静-高脂组、高脂运动-高脂组、高脂安静-普食组、高脂运动-普食组,分别给予6周高脂喂养或普食喂养。子代在第10周进行葡萄糖耐量试验与胰岛素耐量试验,随后进行体成分分析及取材。肝脏蛋白免疫印迹测定p-Akt水平;下丘脑弓状核免疫荧光分析神经肽Y和阿黑皮素的表达情况。结果与结论:①在高脂饮食模式下,与高脂安静组相比,高脂运动组子代小鼠的糖代谢能力、体质量、体成分等都有显著性改善(P<0.05);②在普食饮食模式下,与高脂安静组相比,高脂运动组子代小鼠下丘脑弓状核的神经肽Y表达量显著下降(P<0.05),阿黑皮素表达显著上调(P<0.05),肝脏Akt(Ser473)磷酸化蛋白表达在胰岛素(-)的情况下无显著性差异,但在胰岛素(+)的情况下组间差异有显著性意义(P<0.05);③结果说明,子代在高脂模式下,母体长期运动获得的代谢保护效应可能会随着子代高脂暴露时间的延长而逐渐弱化;子代在普食模式下,母代长期的运动可以改善雄性子代能量代谢的中枢调控和胰岛素的敏感性。

高脂饮食诱导胰岛素抵抗过程中肝脏能量代谢特征的研究

本研究旨在通过建立胰岛素抵抗全过程的小鼠模型,研究在这个过程中,肝内线粒体功能和能量代谢的变化情况。试验选取60只雄性C57BL6小鼠,随机选取30只饲喂普通维持饲料作为对照组(Con组),另外30只饲喂高脂饲料作为高脂饮食组(HFD组)进行造模,分别于饲喂的第4、6、8、10和12周,各组随机选取6只小鼠进行处理,经胰岛素抵抗评估和病理组织学检查确认成功建立胰岛素抵抗全过程的模型。在第8和12周,采集鼠尾血液,进行葡萄糖耐受试验(glucose tolerance tests,IGTT)和胰岛素耐受试验(insulin tolerance tests,ITTs)。在第4、6、8、10和12周,采集小鼠的血清和肝组织样品进行试验:1)检测空腹血糖和血清含量;2)ELISA法检测肝组织中的Srebp-1c酶、PFK1和COX-Ⅰ含量;3)生化检测血清中的ALT和AST含量;4)Western blot法检测肝组织中的PI3K、Akt、P-Akt、GLUT4、GSK-3β、P-GSK-3β、FOXO1、P-FOXO1、SIRT1、AMPK、P-AMPK、PGC-1α蛋白表达量;5)采用透射电镜、HE染色、油红O染色、PAS染色检测肝病理组织和结构的变化。结果表明:1)12周的高脂日粮引起小鼠肥胖、HOMA-IR增加,油红O染色显示,明显的脂肪沉积,成功诱导小鼠胰岛素抵抗全过程模型;2)胰岛素抵抗过程中,小鼠ALT和AST增加,HE结果显示,明显的脂滴空泡、肝细胞结构紊乱;3)在饲喂高脂日粮的第4周之后,肝胰岛素上游信号开始受到影响;4)与Con-6组相比,HFD-6组小鼠肝内的GLUT4蛋白表达量和P-FOXO1/FOXO1比值、PFK1含量显著下降(P<0.01);与Con-4组相比,HFD-4组小鼠肝内的GSK-3β磷酸化、Srebp-1c酶水平逐渐降低(P<0.05);PAS结果显示从第8周开始,HFD组小鼠肝细胞内糖原含量减少;5)与Con-4组相比,HFD-4组小鼠肝的AMPK、P-AMPK、SIRT1含量显著降低(P<0.01和P<0.001);6)HFD组小鼠肝中Mfn2在第10周出现上升,Drp1蛋白的表达呈现先降低后升高的趋势;7)与HFD-6组相比,HFD-6组小鼠肝中的PINK1和Parkin蛋白明显下降(P<0.05)。综上表明,肝作为代谢的主要器官,在饲喂60%高脂饲料后,会发生选择性胰岛素抵抗,在抵抗后整体上能量分解代谢减弱、线粒体损伤增强,而清除损伤线粒体的自噬功能却减弱,另外在第8、10周时出现了短暂的线粒体生物发生与融合增强现象,说明由于肝能量缺乏导致了短暂的代偿作用。本研究从发生全过程的角度阐释肝胰岛素抵抗中的能量代谢特征和规律,为进一步深入研究营养过剩影响细胞能量代谢的机制提供参考。

2型糖尿病患者胰岛素抵抗与尿酸/高密度脂蛋白胆固醇比值的相关性研究

目的探讨2型糖尿病(T2DM)患者胰岛素抵抗与尿酸/高密度脂蛋白胆固醇比值(UHR)的相关性。方法本研究为一项前瞻性研究,收集2021年1月1日至2024年3月1日于滁州市中西医结合医院内分泌科治疗的T2DM患者98例,根据稳态模型胰岛素抵抗指数(HOMA-IR)将所有患者分为胰岛素抵抗组(n=38)和非胰岛素抵抗组(n=60)。比较两组患者的临床参数(年龄、性别、体重指数、病程、吸烟史、饮酒史、高血压史)和生化指标[空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗、总胆固醇、甘油三脂、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿酸、肌酐]水平。采用Pearson相关性分析胰岛素抵抗与生化指标之间的相关性,多因素Logistic回归分析胰岛素抵抗的危险因素。结果胰岛素抵抗组患者的年龄、体重指数、合并高血压比率分别为(55.92±13.28)岁、(24.17±5.36)kg/m^(2)、47.37%,均明显高于非胰岛素抵抗组[(62.51±12.73)岁、(27.92±4.81)kg/m^(2)、26.67%],差异均有统计学意义(P<0.05)。胰岛素抵抗组患者的空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗、甘油三脂、LDL-C、尿酸、肌酐及UHR水平分别为(11.01±4.10)mmol/L、(9.83±2.41)%、(10.74±4.99)μIU/mL、5.11±2.83、(2.31±1.34)mmol/L、(2.98±1.45)mmol/L、(439.87±90.56)μmol/L、(103.06±54.25)μmol/L、(22.92±8.72)%,均明显高于非胰岛素抵抗组[(6.99±1.73)mmol/L、(7.35±2.26)%、(4.60±1.59)μIU/mL、2.34±1.30、(0.97±0.25)mmol/L、(2.01±1.27)mmol/L、(357.98±89.74)μmol/L、(69.42±27.81)μmol/L、(16.53±7.32)%],血清HDL-C水平为(0.89±0.41)mmol/L,明显低于非胰岛素抵抗组[(1.21±0.35)mmol/L],差异均有统计学意义(P<0.05);两组总胆固醇比较,差异无统计学意义(P>0.05)。Pearson相关性分析显示胰岛素抵抗与体重指数、空腹血糖、糖化血红蛋白、空腹胰岛素、甘油三脂、LDL-C、肌酐及UHR呈正相关,与HDL-C呈负相关(P<0.05)。多因素Logistic回归分析显示体重指数、UHR是T2DM患者胰岛素抵抗的独立危险因素(P<0.05)。结论胰岛素抵抗的T2DM患者UHR水平明显升高,UHR与胰岛素抵抗呈正相关关系,UHR是T2DM患者发生胰岛素抵抗的危险因素。

转录因子EB在有氧运动改善高脂饮食诱导小鼠骨骼肌胰岛素抵抗中的作用

目的:探讨转录因子EB(TFEB)在有氧运动改善骨骼肌胰岛素抵抗中的作用。方法:18只6周龄雄性SPF级别C57BL/6小鼠随机分为普通膳食组(CON组)、高脂膳食组(HFD组)和高脂膳食运动组(HFDE组),每组6只。喂养12周后HFDE组小鼠进行12周跑台运动(60 min/次、5次/周,速度12 m/min,坡度0°)。然后采用腹腔注射葡萄糖耐量试验(IPGTT)和腹腔注射胰岛素耐量试验(IPITT)分别检测小鼠葡萄糖耐量和胰岛素耐量,生化检测小鼠空腹血糖和胰岛素含量、计算胰岛素抵抗指数(HOMA-IR),评价小鼠胰岛素抵抗水平;蛋白质印迹法(WB)检测骨骼肌胞核和胞质磷酸化TFEB(pTFEB)、TFEB蛋白表达、胞质和胞膜葡萄糖转运体4(GLUT4)蛋白表达、骨骼肌胰岛素信号通路磷酸化胰岛素受体底物1(pIRS1)、磷酸化蛋白激酶B(p AKT)、磷脂酰肌醇-3-激酶(PI3K)和pTBC1D4(又名AS160)的蛋白表达;分别对p TFEB、TFEB和胰岛素信号通路相关蛋白做相关性分析。结果:(1)与CON组相比,HFD组小鼠体重、IPGTT、IPITT各个时间点血糖、曲线下面积(AUC)、血清胰岛素、HOMA-IR、胞质pTFEB、总TFEB(TTFEB)和GLUT4蛋白表达均显著增加(P<0.01),但骨骼肌pIRS1、pAKT、PI3K、pTBC1D4、胞膜GLUT4蛋白表达均显著下降(P<0.01),胞核pTFEB和T-TFEB蛋白表达均无显著性差异(P>0.05)。(2)与HFD组相比,HFDE组小鼠体重、IPGTT各个时间点血糖、AUC、IPITT的0 min、30 min、60 min的血糖及AUC、血清胰岛素、HOMA-IR、骨骼肌胞质p TFEB、T-TFEB、GLUT4蛋白表达均显著下降(P<0.05或P<0.01),但pIRS1、pAKT、PI3K、p TBC1D4、胞膜GLUT4和胞核T-TFEB蛋白表达均显著增加(P<0.01)。(3)TFEB与胰岛素信号通路蛋白相关性分析结果显示,胞质p TFEB与pIRS1、PI3K、pAKT和pTBC1D4蛋白表达呈负相关(r=-0.8642,r=-0.7789,r=-0.8946,r=-0.8040,P<0.01),与胞质GLUT4呈正相关(r=0.8532,P<0.01);胞核TFEB与胞膜GLUT4蛋白表达呈正相关(r=0.7744,P<0.01)。结论:高脂膳食可引起小鼠骨骼肌胰岛素信号通路相关蛋白表达下降,胰岛素作用减弱,导致糖、脂代谢紊乱;有氧运动可显著增加高脂膳食小鼠骨骼肌胰岛素信号通路相关蛋白表达,促进胰岛素功能,有效改善高脂膳食小鼠胰岛素敏感性和糖、脂代谢紊乱,其机制可能是有氧运动促进骨骼肌TFEB核转位,激活IRS1/PI3K/AKT/TBC1D4/GLUT4信号通路和增加细胞膜GLUT4表达,增强骨骼肌细胞葡萄糖摄取能力。TFEB介导的胰岛素信号通路可能是有氧运动改善骨骼肌胰岛素抵抗的重要信号通路。

胰岛素联合大剂量维生素D治疗GDM对患者血清vaspin、Visfatin水平及妊娠结局的影响

目的:研究大剂量维生素D联合胰岛素对妊娠期糖尿病(GDM)孕妇血清内脏脂肪特异性丝氨酸蛋白酶抑制因子(vaspin)、内脏脂肪素(Visfatin)水平及妊娠结局的影响。方法:将本院2021年12月-2023年3月收治的GDM孕妇105例随机数字表法分为联合组(n=53例)与对照组(n=52例),除调整饮食、运动外,两组均接受门冬胰岛素治疗,联合组联合大剂量维生素D补充治疗,持续4周,比较治疗前、治疗4周后两组糖脂代谢、胰岛素抵抗、血25羟基维生素D3[25(OH)D3]、脂肪因子变化,均随访至妊娠结束,比较两组妊娠结局及不良反应。结果:治疗后,联合组空腹血糖(5.26±0.53 mmol/L)、餐后2h血糖(6.62±0.78 mmol/L)、糖化血红蛋白(5.12±0.6)%、总胆固醇(3.24±0.56 mmol/L)、甘油三酯(2.96±0.53 mmol/L)、低密度脂蛋白胆固醇(2.51±0.55 mmol/L)、空腹胰岛素(12.52±2.63 mU/L)、胰岛素抵抗指数(2.12±0.14)、vaspin(23.15±2.74 ng/ml)和Visfatin(102.56±20.27 ng/ml)均低于对照组,25(OH)D3(26.52±5.71 ng/ml)高于对照组(均P <0.05)。联合组自然分娩率(75.5%)高于对照组(55.8%),剖宫产率(15.1%)、巨大儿发生率(3.8%)均低于对照组(32.7%、15.4%)(均P<0.05);两组不良反应(7.5%比5.8%)无差异(P>0.05)。结论:胰岛素联合大剂量维生素D治疗GDM对患者调节糖脂代谢作用显著,推测其可通过下调vaspin、Visfatin,升高25(OH)D3水平,减轻胰岛素抵抗,改善妊娠结局。

优质干预在老年2型糖尿病患者胰岛素注射治疗中的应用价值分析

目的探讨优质干预在胰岛素注射治疗老年2型糖尿病(type 2 diabetes mellitus,T2DM)中的应用价值。方法回顾性选取2023年5月—2024年4月贵州省黔南州人民医院收治的90例老年T2DM患者的临床资料,根据不同的护理方法分为两组,各45例。对照组进行常规护理干预,观察组在对照组的基础上进行优质干预,比较两组血糖指标、知信行表现。结果观察组空腹血糖、餐后2 h血糖、糖化血红蛋白均低于对照组,差异有统计学意义(P均<0.05)。观察组知识、信念、行为评分及总分均高于对照组,差异有统计学意义(P均<0.05)。结论老年2型糖尿病胰岛素注射治疗期间,优质干预有利于降低患者的血糖水平,且对患者知信行表现改善具有积极影响。

术前血清HDL-C、IGF-1水平对前列腺癌根治术患者预后的预测价值研究

目的探讨术前血清高密度脂蛋白胆固醇(HDL-C)、胰岛素样生长因子-1(IGF-1)对前列腺癌根治术患者预后的预测价值。方法回顾性选取2017年8月至2021年10月安徽医科大学附属阜阳医院治疗的90例前列腺癌患者的临床资料,分析患者术前血清HDL-C、IGF-1水平。术后对患者随访1年,评估患者预后情况,分析术前血清HDL-C、IGF-1水平对前列腺癌根治术患者预后的预测价值。结果90例前列腺癌根治术患者中预后不良20例,占比为22.22%。不同预后患者血清IGF-1、HDL-C、总胆固醇、空腹血糖水平比较,差异具有统计学意义(P<0.05)。经Logistic回归分析显示,血清HDL-C、IGF-1是前列腺癌根治术患者预后的影响因素(P<0.05);受试者工作特征(ROC)曲线显示,血清HDL-C、IGF-1单独及联合对前列腺癌根治术患者预后均有一定的预测价值,且联合预测价值更高。结论血清HDL-C、IGF-1可对前列腺癌根治术患者预后产生影响,且术前血清HDL-C与IGF-1联合检测对前列腺癌根治术患者预后具有较高的预测价值。

Bcl-2、Bax、Insulin在高脂诱导C57BL/6J小鼠胰岛损伤中的表达

目的探讨细胞凋亡因子在高脂引起的小鼠胰岛损伤中的表达。方法雄性C57BL/6J小鼠分高脂饮食组(HFD)和低脂饮食对照组(LFD),每组6只,喂养12周时尾部取血进行葡萄糖耐量实验(GTT)及胰岛素耐量实验(ITT)检测胰岛功能。持续喂养至20周时处死取胰腺组织用于透射电镜,苏木素-伊红(haematoxylineosin,HE)染色观察胰岛形态;免疫组化(immunohistochemical,IHC)检测Bcl-2、Bax及Insulin蛋白表达水平。结果喂养12周后,小鼠GTT和ITT显示,HFD组小鼠葡萄糖负荷时的血糖水平高于LFD组(P<0.05)。注射胰岛素后,HFD组小鼠血糖下降缓慢且血糖水平仍较LFD组高(P<0.05)。HE结果显示HFD组小鼠胰岛数量和体积较LFD组减少,形态损伤严重。电镜下观察HFD组胰岛β细胞超微结构受损较LFD组严重,HFD组β细胞形态不规则,细胞核固缩,染色质边集,有大量电子密度较小的脂滴堆积,其中胰岛细胞胞浆内胰岛素分泌颗粒减少。免疫组化的结果显示:HFD组Bcl-2表达低于低脂组,同时HFD组Bax表达高于LFD组,而HFD组胰岛中的Insulin表达低于LFD组(P<0.01)。结论高脂导致C57BL/6J小鼠胰岛细胞结构功能损伤,影响胰岛素的合成与分泌,并且增加细胞凋亡。Bcl-2及Bax在胰岛细胞凋亡中起一定的作用,并可能与高脂饮食有关。

代谢组学联合网络药理学分析香蜂草苷缓解非酒精性脂肪肝大鼠的作用机制

目的:利用非靶向代谢组学联合网络药理学研究香蜂草苷改善非酒精性脂肪性肝病(NAFLD)脂代谢的作用机制。方法:将大鼠随机分为正常组、模型组和香蜂草苷组。模型组与香蜂草苷组给予高脂饮食(HFD)8周诱导NAFLD动物模型。灌胃给药,连续8周。采用苏木精—伊红(HE)、油红染色观察细胞形态和脂质堆积情况。用高分辨液相色谱—质谱(UPLCQTOF/MS)对大鼠肝组织进行代谢组学检测,并利用KEGG数据库分析代谢通路。采用网络药理学对香蜂草苷与NAFLD共同作用的靶点进行预测,并联合代谢组学进一步分析潜在的靶点。结果:香蜂草苷明显减轻大鼠肝损伤、抑制肝脏脂质的过度沉积;正交偏最小二乘判别分析(OPLS-DA)分析显示组间的代谢物有显著差异,火山图显示正常组与模型组存在404个差异代谢物(上调293个,下调111个),模型组与香蜂草苷组存在147个差异代谢物(上调95个,下调52个);代谢通路分析显示差异代谢物主要富集于鞘脂代谢通路;网络药理学筛选药物与疾病共同靶点共139个,联合代谢组学和网络药理学分析显示,香蜂草苷可通过调节TNF、Bcl2、Mapk8、Pik3ca、Akt1、mTOR、Gsk3β来调控鞘脂代谢通路和胰岛素抵抗。结论:香蜂草苷能够通过鞘脂代谢通路和胰岛素抵抗调节脂质代谢紊乱从而发挥治疗NAFLD的作用。

High dietary fructose intake: Sweet or bitter life?

Epidemiological data show that the consumption of added sugars as ingredients in processed or prepared foods and caloric beverages has dramatically increased. Fructose and fructose-based sweeteners are the most commonly added sugars and high-fructose corn syrup (HFCS-55: 55% fructose, 42% glucose and 3% higher saccharides) accounts for over 40% of all added caloric sweeteners. Concerns regarding the health risk of added sugar follow the demonstration that the consumption of foods and beverages high in sugars is associated with an increased prevalence of obesity, insulin resistance, dyslipidemia and, more recently, ischemic heart and kidney diseases. The molecular mechanism(s) underlying the detrimental effects of sugar are not completely understood and their elucidation is critical to provide new insights on the health risk of fructose-based sweeteners. A better understanding of the key role of fructose overconsumption in the development of metabolic disorders may contribute to planning new strategies for preventing deleterious dietary behaviors from becoming established and, thus, curbing the rise in the number of insulin-resistant, obese and diabetic populations worldwide.

High density lipoproteins and type 2 diabetes:Emerging concepts in their relationship

Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.

Dual probiotic strains suppress high fructose-induced metabolic syndrome

AIM:To investigate the effect of novel probiotics on the clinical characteristics of high-fructose induced metabolic syndrome.METHODS:Male Wistar rats aged 4 wk were fed a 70% w/w high-fructose diet(n = 27) or chow diet(n = 9) for 3 wk to induce metabolic syndrome,the rats were then randomized into groups and administered probiotic [Lactobacillus curvatus(L.curvatus) HY7601 and Lactobacillus plantarum(L.plantarum) KY1032] at 109 cfu/d or 1010 cfu/d or placebo by oral gavage for 3 wk.Food intake and body weight were measured once a week.After 6 wk,the rats were fasted for 12 h,then anesthetized with diethyl ether and sacrificed.Blood samples were taken from the inferior vena cava for plasma analysis of glucose,insulin,C-peptide,totalcholesterol,triglycerides and thiobarbituric acid-reacting substances.Real-time polymerase chain reaction was performed using mouse-specific Taqman probe sets to assess genes related to fatty acid β-oxidation,lipogenesis and cholesterol metabolism in the liver.Target gene expression was normalized to the housekeeping gene,glyceraldehyde-3-phosphate dehydrogenase.RESULTS:Rodents fed a high-fructose diet developed clinical characteristics of the metabolic syndrome including increased plasma glucose,insulin,triglycerides,total cholesterol and oxidative stress levels,as well as increased liver mass and liver lipids compared to chow fed controls.Probiotic treatment(L.curvatus HY7601 and L.plantarum KY1032) at high(1010 cfu/d) or low dosage(109 cfu/d) lowered plasma glucose,insulin,triglycerides and oxidative stress levels.Only high-dose probiotic treatment reduced liver mass and liver cholesterol.Probiotic treatment reduced lipogenesis via downregulation of SREBP1,FAS and SCD1 mRNA levels and increased β-oxidation via up-regulation of PPARα and CPT2 mRNA levels.CONCLUSION:Probiotic L.curvatus HY7601 and L.plantarum KY1032 combined suppressed the clinical characteristics of high-fructose-induced metabolic syndrome,therefore,may provide a natural alternative for the treatment of diet-induced metabolic syndrome.