Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

Outcomes of total pancreatectomy with islet autotransplantation:A systematic review and meta-analysis

BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.

Islet transplantation-immunological challenges and current perspectives

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity

Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.

A pancreatic player in dementia:pathological role for islet amyloid polypeptide accumulation in the brain

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.

Microbiological cultures and antimicrobial prophylaxis in patients undergoing total pancreatectomy with islet cell autotransplantation

To the Editor:Total pancreatectomy with islet cell autotransplantation(TPIAT)is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic pancreatitis.This procedure involves surgical removal of the entire pancreas,isolation of islet cells and reinfusion of these cells into the liver via portal vein[1,2].The risk of contamination to the final islet cell product can occur at several stages of the isolation procedure[3].In order to ensure the sterility of the islet cell product,multiple samples from the preservation and cannulation solution,and the final islet cell product are sent for bacterial cultures.Prior studies have found variable clinical consequences of these cultures on infectious com-plications or graft function[3-9].Herein we aimed to determine the incidence of infection in 60 days post-TPIAT and its association with the culture data.

Advances in microfluidic chips based on islet hormone-sensing techniques

Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of islets,and serves an important role in the homeostasis of blood glucose.Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes.Therefore,it is crucial to develop accurate,real-time,laborsaving,high-throughput,automated,and cost-effective techniques for the sensing of islet secretome.Microfluidic chips,an elegant platform that combines biology,engineering,computer science,and biomaterials,have attracted tremendous interest from scientists in the field of diabetes worldwide.These tiny devices are miniatures of traditional experimental systems with more advantages of timesaving,reagent-minimization,automation,high-throughput,and online detection.These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years.In this review,we present a brief introduction of microfluidic chips,and three microfluidic chipsbased islet hormone sensing techniques.We focus mainly on the theory of these techniques,and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma

BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma(PDAC)have not been specifically addressed.AIM To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences(proximal vs distal residual pancreas)are associated with islet amyloid deposition.METHODS We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients,including 14 patients with normal glucose tolerance(NGT),16 patients with prediabetes and 15 new-onset diabetes(NOD)patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020.Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans.Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows:(1)Hematoxylin and eosin for general histological appearance;(2)hematoxylin and insulin for the determination of fractionalβ-cell area(immunohistochemistry);and(3)quadruple insulin,glucagon,thioflavin T and DAPI staining for the determination ofβ-cell area,α-cell area and amyloid deposits.RESULTS Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition,fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions,especially in the prediabetes and NOD groups.Consistent with this finding,the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group(37.35±12.16 cm^(3) vs 69.79±18.17 cm^(3),P<0.001).As expected,islets that stained positive for amyloid(islet amyloid density)were found in the majority of PDAC cases.The proportion of amyloid/islet area(severity of amyloid deposition)was significantly higher in both prediabetes and NOD patients than in NGT patients(P=0.002;P<0.0001,respectively).We further examined the regional differences in islet amyloid deposits.Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups(3.98%±3.39%vs 0.50%±0.72%,P=0.01;12.03%vs 1.51%,P=0.001,respectively).CONCLUSION In conclusion,these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation,which may be associated with the pathogenesis of NOD secondary to PDAC.

Human pluripotent stem cell-derivedβcells:Truly immature isletβcells for type 1 diabetes therapy?

A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.

A Study on Enhancing Pancreatic Islet Function in Type 2 Diabetes and Coronary Heart Disease Patients with Liraglutide and Metformin Combination Therapy

Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.

西藏门巴族人群胰岛细胞功能、脂质代谢、炎症反应与中医体质的相关性研究

目的探讨西藏门巴族人群胰岛细胞功能、脂质代谢和炎症反应与中医体质的相关性。方法选取2023年1月—2023年6月墨脱村、亚东村、朗杰岗村、巴日村、德吉村、玛迪村6个门巴族乡的门巴族人群进行调查,共计237例。分析人群中医体质分布情况,同时比较前三位中医体质人群的胰岛细胞功能、脂质代谢和炎症因子水平。结果中医体质类型中以痰湿质、湿热质和气虚质为主,分别占32.07%、26.16%和18.57%。痰湿质组、湿热质组和气虚质组性别、年龄、体质量指数比较,差异均无统计学意义(P>0.05)。湿热质组空腹血糖和胰岛素抵抗指数分别为(4.98±0.83)mmol/L和(1.75±0.32),均低于痰湿质组和气虚质组(P<0.05),湿热质组胰岛β细胞功能指数为(94.45±9.11),均高于痰湿质和气虚质组(P<0.05);湿热质组总胆固醇和甘油三酯分别为(3.98±0.99)mmol/L和(1.02±0.29)mmol/L,均低于痰湿质组和气虚质组(P<0.05),湿热质组高密度脂蛋白胆固醇为(1.26±0.20)mmol/L,均高于痰湿质组和气虚质组(P<0.05)。痰湿质、湿热质和气虚质组血清白细胞介素-6、超敏c反应蛋白、肿瘤坏死因子-α比较,差异均无统计学意义(P>0.05)。结论西藏门巴族人群中医体质以痰湿质、湿热质和气虚质为主,其中湿热质人群胰岛细胞功能、脂质代谢优于痰湿质和气虚质人群,炎症因子比较无差异。

青钱柳多糖调节胰岛和肝脏葡萄糖转运蛋白4转位干预2型糖尿病大鼠的作用机制

目的 观察青钱柳多糖调节胰岛和肝脏葡萄糖转运蛋白4(GLUT4)转位改善2型糖尿病(T2DM)大鼠外周胰岛抵抗的作用。方法 建立T2DM大鼠模型(给予高脂饲料后注射链脲佐菌素35 mg·kg^(-1)),将造模成功的大鼠随机分为模型对照组,青钱柳多糖提取物小、大剂量组(5,10 g·kg^(-1))和盐酸二甲双胍组(0.25 g·kg^(-1)),每组9只,给药8周。测定空腹血糖、血脂变化;苏木精-伊红染色法观察胰岛和肝脏病理形态的改变;免疫组化法观察胰岛磷酸化磷酯酰肌醇3激酶(p-PI3K)、磷酸化丝氨酸苏氨酸蛋白激酶1(p-Akt1)、GLUT4蛋白的表达;免疫荧光观察肝脏和胰岛GLUT4转位。结果 与模型对照组比较,青钱柳多糖提取物小、大剂量组和盐酸二甲双胍组大鼠胰岛和肝脏结构较完整,血糖下降(P<0.05),高密度脂蛋白升高(P<0.05),胰岛p-PI3K、p-Akt1、GLUT4蛋白表达升高(P<0.05),肝脏和胰岛GLUT4转位增强(P<0.05)。结论 青钱柳多糖可调节T2DM大鼠糖脂紊乱,其机制可能是增强胰岛p-PI3K、p-Akt1、GLUT4蛋白的表达,促进肝脏和胰岛GLUT4转位,从而调节外周胰岛抵抗。

益气养阴汤加减联合达格列净、二甲双胍对初诊2型糖尿病患者的疗效及血压、血尿酸水平的影响

目的:观察益气养阴汤加减联合达格列净、二甲双胍对初诊2型糖尿病(T2DM)的疗效及对患者血压、血尿酸(UA)水平的影响。方法:将2020年3月—2023年3月于仙桃市第一人民医院就诊且符合纳入条件的92例初诊T2DM患者作为对象,根据随机数字表法分为西药组和中西结合组。西药组45例给予达格列净、二甲双胍治疗,中西结合组47例给予益气养阴汤加减联合达格列净、二甲双胍治疗,两组均治疗12周。检测并比较两组胰岛功能指标、糖代谢指标、血压指标及血尿酸(UA)、载脂蛋白B/A1(ApoB/A1)、白脂素(Asprosin)水平,统计两组不良反应情况。结果:治疗前,两组胰岛功能指标、糖代谢指标、血压指标比较,差异无统计学意义(P>0.05)。治疗后,两组胰岛素样生长因子1(IGF-1)、胰岛β细胞功能指数(HOMA-β)升高(P<0.01),中西结合组高于西药组(P<0.01);两组糖代谢指标、胰岛素抵抗指数(HOMA-IR)、血压指标降低(P<0.05,P<0.01),中西结合组低于西药组(P<0.05,P<0.01);两组血压指标比较,差异无统计学意义(P>0.05)。治疗前,两组UA、Apo-A1、Asprosin比较,差异无统计学意义(P>0.05)。治疗后,两组UA、Apo-A1、Asprosin降低(P<0.05,P<0.01),中西结合组低于西药组(P<0.05,P<0.01)。治疗前,两组中医证候评分(包括3项主症和5项次症)比较,差异无统计学意义(P>0.05)。治疗后,两组3项主症和5项次症评分降低(P<0.01),中西结合组低于西药组(P<0.01)。西药组发生低血糖2例,胃肠道反应和生殖道感染各1例,中西结合组发生胃肠道反应2例。两组不良反应比较,差异无统计学意义(P>0.05)。结论:益气养阴汤加减联合达格列净、二甲双胍治疗初诊T2DM可有效控制血糖和血压,调节UA、Apo-A1、Asprosin的表达,改善胰岛功能,且不增加其不良反应。

玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病气阴两虚证患者临床疗效观察

目的:对玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病(T2DM)气阴两虚证患者的临床疗效进行探讨。方法:将60例T2DM患者随机分为对照组(n=30)和观察组(n=30),对照组采用二甲双胍联合德谷门冬双胰岛素治疗,观察组在此基础上应用玉液汤加减治疗,比较2组治疗后的中医证候积分、糖化血红蛋白(Hb Alc)、空腹血糖(FPG)、餐后2 h血糖(2h PG)、日内平均血糖波动幅度(MAGE)、胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-IS)。结果:治疗后,观察组总有效率显著高于对照组(93.33%vs 86.67%);观察组中医证候积分、Hb Alc、FPG、2h PG、MAGE和HOMA-IR等指标均低于对照组,HOMA-IS高于对照组(均P<0.05)。结论:玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病气阴两虚证患者疗效显著,可有效控制患者的血糖并改善胰岛功能。

枸橼酸氯米芬+二甲双胍对多囊卵巢综合征不孕症患者的疗效及其性激素水平的影响

目的探究多囊卵巢综合征不孕症的联合疗法,分析枸橼酸氯米芬、二甲双胍联用的价值。方法随机选取滕州市妇幼保健院于2022年3月—2023年6月收治的60例多囊卵巢综合征不孕症患者为研究对象,经信封法分为对照组(n=30,枸橼酸氯米芬治疗)、观察组(n=30,枸橼酸氯米芬+二甲双胍治疗),比较两组性激素、血糖及胰岛功能、排卵率、妊娠率、治疗有效率、不良反应发生率。结果治疗后,观察组性激素、血糖及胰岛功能、排卵率、妊娠率、治疗有效率均优于对照组,差异有统计学意义(P均<0.05);两组不良反应发生率(13.33%vs 10.00%)对比,差异无统计学意义(χ^(2)=0.162,P=0.688)。结论多囊卵巢综合征不孕症联合应用枸橼酸氯米芬、二甲双胍治疗具有显著效果,可有效改善患者的性激素、血糖、胰岛功能、排卵情况及妊娠情况,保障临床治疗安全性。

全程超声引导下经皮门静脉穿刺胰岛移植术的护理

目的 总结糖尿病患者实施全程超声引导下经皮门静脉穿刺胰岛移植术的护理要点,为该类患者提供护理经验。方法 本院于2017年12月至2023年9月对27例(44例次)患者进行了全程超声引导下经皮门静脉穿刺置管胰岛移植术,并配合做好术前、术中、术后护理工作。结果 27例(44例次)患者均顺利完成手术。其中3例次(6.8%)术中出现上腹部及肝区疼痛、恶心呕吐,8例次(18.2%)术中出现门静脉压力一过性升高,6例次(13.6%)拔除门静脉插管后发生活动性出血;术后所有患者均无迟发性门静脉活动性出血、门静脉血栓形成等并发症。结论 术前访视患者了解病情,做好心理护理和相关疾病知识宣教工作;术中密切监测患者生命体征、门静脉压力及血糖,预防并发症发生;术后预防门静脉活动性出血,对确保超声引导下经皮门静脉穿刺胰岛移植术顺利完成具有重要作用。

甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果观察

目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加甘精胰岛素U300治疗,持续治疗3个月,对比2组血糖及相关指标变化,并监测患者胰岛素功能相关指标改善情况,评估低血糖反应等不良反应情况。结果治疗后,U300组血糖指标、血糖波动指标均显著低于非甘精组,差异有统计学意义(P<0.05)。U300组治疗后胰岛素功能指标均显著优于非甘精组,空腹及餐后2 h C肽均显著高于非甘精组,差异有统计学意义(P<0.05)。U300组低血糖反应发生率(2.50%,1/40)和不良反应总发生率(20.00%,8/40)与非甘精组(2.56,1/39;17.95%,7/39)比较,差异无统计学意义(P>0.05)。结论增加甘精胰岛素U300治疗,可更好地提升患者血糖管理效果,并可改善胰岛功能,有利于稳定控制血糖,有助于提高患者病情控制效果,应用效果安全可靠。

达格列净联合阿托伐他汀治疗糖尿病肾病的效果及对患者胰岛功能和机体微炎症状态的影响

目的探究达格列净联合阿托伐他汀治疗糖尿病肾病(DN)的效果及对患者胰岛功能和机体微炎症状态的影响。方法选取2021年2月至2022年2月海南省海口市人民医院收治的DN患者116例,按随机数字表法分为对照组和观察组,各58例。对照组采用阿托伐他汀钙片治疗,观察组在对照组基础上联合达格列净片治疗,2组均治疗3个月。比较治疗总有效率,治疗前后肾功能、胰岛功能指标和炎症因子水平。结果观察组总有效率显著高于对照组[93.1%(54/58)比77.6%(45/58)],差异有统计学意义(χ^(2)=5.583,P=0.018)。治疗后2组血尿素氮、血肌酐、24 h尿蛋白定量均明显低于治疗前,且观察组均低于对照组,差异均有统计学意义(均P<0.001)。治疗后2组稳态模型胰岛素抵抗指数均显著低于治疗前且观察组低于对照组[(2.43±0.28)比(2.67±0.31)],稳态模型胰岛β细胞功能指数均显著高于治疗前且观察组高于对照组[(13.4±3.8)比(10.5±3.3)],差异均有统计学意义(均P<0.05)。治疗后2组白细胞介素6、肿瘤坏死因子α、高敏C反应蛋白水平均显著低于治疗前且观察组低于对照组,差异均有统计学意义(均P<0.05)。结论达格列净联合阿托伐他汀治疗DN临床效果较好,可以有效改善患者胰岛功能,减轻机体的微炎症状态。

小鼠Islet-1基因慢病毒表达载体的构建及其诱导C_3H_(10)T1/2细胞向心肌样细胞特异性分化

目的研究Islet-1对干细胞分化的影响。方法用PCR钓取目的基因,将目的基因与pLenO-WPI载体连接,选取阳性质粒,与辅助质粒共同感染293T细胞生产出慢病毒载体。感染C3H10T1/2细胞,实时荧光定量PCR及Western blot检测Islet-1和心肌、肝脏、骨骼及神经各系统相关标志物的表达,免疫荧光检测心肌肌钙蛋白T(cTnT)表达部位。结果 PCR及测序显示目的片段正确插入,实验组有Islet-1表达;心肌早期发育相关基因GATA-4、MEF2C、NKx2.5在检测到荧光蛋白1周后升高,2周到达高峰,3周后可检测到心肌特异性蛋白cTnT(0.582±0.0576),其时序性表达呈随时间增强趋势;cTnT表达于胞质;肝脏系统特异性标志AFP及ALB、骨骼系统特异性标志BGP及BALP、神经系统特异性标志Nestin及GFAP均未表达。结论 Islet-1具有特异性促进干细胞向心肌样细胞分化的作用。

小鼠Islet-1基因RNAi慢病毒载体的构建

目的构建高效沉默小鼠Islet-1基因的慢病毒载体。方法针对小鼠Islet-1基因设计3个RNAi靶序列,合成相应的短发卡RNA(shRNA)寡核苷酸序列(oligo):Sh1、Sh2、Sh3,分别插入经酶切后的PLVTHM载体。经PCR和测序方法筛选阳性克隆,抽提阳性克隆质粒经大肠埃希菌扩增后,与其辅助包装质粒共同感染293T细胞制备慢病毒载体,利用斑形成试验测定病毒滴度。感染C3H10T1/2细胞株,以流式细胞仪检测其感染效率、荧光定量PCR检测其干扰效率。结果与正常C3H10T1/2细胞比较,测序及PCR结果显示目的片段插入正确;病毒滴度值为3.87×108TU/ml;慢病毒载体对C3H10T1/2细胞感染效率达90.36%;3个靶点(抑制效率分别为76.8%5、5.1%和11.7%)均有干扰效果,与正常细胞比较,Sh1靶点干扰效果最为显著(76.8%,P<0.05)。结论成功构建高效沉默Islet-1基因慢病毒载体。