APOA2 ?256T>C polymorphism interacts with saturated fatty acids intake to affect anthropometric and hormonal variables in type 2 diabetic patients

Recent studies have established the interaction between APOA2 −256T>C polymorphism and dietary saturated fatty acids intake in relation to obesity on healthy individuals. In the current study, we investigate the effects of this interaction on anthropometric variables and serum levels of leptin and ghrelin in patients with type 2 diabetes. In this cross-sectional study, 737 patients with type 2 diabetes mellitus (290 males and 447 females) were recruited from diabetes clinics in Tehran. The usual dietary intake of all participants during the last year was obtained by validated semiquantitative food frequency questionnaire. APOA2 genotyping was performed by real-time PCR on genomic DNA. No significant relation was obtained by univariate analysis between anthropometric variables and APOA2 genotypes. However, after adjusting for age, gender, physical activity and total energy intake, we identified a significant interaction between APOA2-saturated fatty acids intake and body mass index (BMI). After adjusting for potential confounders, serum levels of ghrelin in CC genotype patients were significantly higher than T allele carriers (p = 0.03), whereas the case with leptin did not reveal a significant difference. The result of this study confirmed the interaction between APOA2 −256T>C polymorphism and SFAs intake with BMI in type 2 diabetic patients. In fact, homozygous patients for the C allele with high saturated fatty acids intake had higher BMI. The APOA2 −256T>C polymorphism was associated with elevated levels of serum ghrelin.     

糖尿病大鼠性腺及外周血中性激素的改变

目的:研究糖尿病大鼠性腺及外周血中性激素的变化。方法:用放射免疫法检测糖尿病(DM)大鼠,正常(NDM)大鼠和STZ大鼠血清性激素含量,同时称取性腺重量,镜检睾丸、前列腺及附睾的组织形态学改变。结果:DM组睾酮水平显著低于NDM组、STZ组(P<0.01);NDM组与STZ组之间,睾酮水平无显著性差异;DM组促黄体生成素(LH)水平显著高于NDM组、STZ组(P<0.01);NDM组与STZ组之间。LH水平无显著性差异;促卵泡刺激素(FSH)水平在各组之间无显著性差异;HE结果显示,DM组性腺显微结构较NDM组及STZ组明显改变。结论:提示DM严重影响大鼠性腺功能及睾酮的合成分泌,并显著降低大鼠血清睾酮含量。     

Diabetes mellitus in the Pima Indians: genetic and evolutionary considerations

Non-insulin-dependent diabetes mellitus is a common disease in the Pima Indians. It is familial and strongly related to obesity. Neel (1962) suggested that the introduction of a steady food supply to people who have evolved a "thrifty genotype" leads to obesity, insulin resistance, and diabetes. Our findings in the Pimas of differences in insulin sensitivity in different metabolic pathways suggest that the thrifty genotype involves the ability of insulin to maintain fat stores despite resistance to glucose disposal. The recent increase in diabetes incidence following the availability of an abundant food supply suggests that the ability to store energy efficiently during cycles of feast and famine may now lead to obesity, insulin resistance, and diabetes.     

脊髓自噬功能激活与大鼠2型糖尿病神经病理性疼痛的关系

目的：探讨脊髓自噬功能与大鼠2型糖尿病神经病理性疼痛（DNP）的关系。方法：雄性SD大鼠（42只）高糖高脂饲养8周,腹腔单次注射链脲佐菌素（STZ）制备大鼠2型糖尿病模型。两周后检测机械缩足阈值（MWT）和热缩足潜伏期（TWL）,降至基础值80%以下者为2型糖尿病神经病理性疼痛大鼠,记为DNP组（24只）;未降至基础值80%以下者为2型糖尿病无神经病理性疼痛大鼠,记为DA组（18只）。另取18只大鼠为对照（control,C）组,普通饲料喂养。于确定DA与DNP分组后的第3、7和14天,测定机械缩足阈值（MWT）和热缩足潜伏期（TWL）,并在行为学检测结束后各组随机取6只大鼠处死,取L4~L6脊髓膨大,采用Western blot法检测自噬特异性蛋白微管相关蛋白1（Beclin-1）、微管相关蛋白1轻链3（LC3）和P62的表达。另取6只7 d DNP组大鼠采用免疫荧光双染法检测脊髓背角P62与小胶质细胞、星形胶质细胞、神经元的共表达情况。结果：连续8周喂养高糖高脂饲料的SD大鼠的血浆胰岛素水平升高,胰岛素敏感指数下调,表明出现胰岛素抵抗;在腹腔注射STZ后,血糖升高达到2型糖尿病诊断标准（≥16.7 mmol/L）;与C组、DA组比较,DNP组大鼠在第3、7和14天时MWT降低,TWL缩短,并且脊髓背角LC3-Ⅱ、Beclin-1表达上调,P62表达下降（P<0.05）。免疫荧光双染色显示,P62在脊髓背角表达,主要与神经元共存,少量与小胶质细胞共存,几乎不与星形胶质细胞共表达。结论：2型糖尿病神经病理性疼痛大鼠脊髓LC3-Ⅱ、Beclin-1和P62表达的改变提示脊髓自噬功能激活;脊髓背角中神经元自噬激活在2型糖尿病大鼠DNP的发生和发展起着关键作用。     

维药罗补甫克比日丸对DM性勃起功能障碍大鼠性激素水平的影响

目的:揭示维药罗补甫克比日丸对糖尿病(DM)性勃起功能障碍(ED)大鼠性激素水平的影响。方法:取50只SD雄性大鼠,从中随机取7只设为正常对照(A)组,余43只行腹腔注射链尿佐菌素(STZ)制造DM动物模型,未成模者为STZ组,成模者用阿朴吗啡(APO)筛选DM性ED模型,并将其随机分为DM性ED对照组、药罗补甫克比日丸(C)组、胰岛素(D)组、联用(E)组,未成ED模者为DM(F)组,共7组。药物干预6周后,检测外周血中性激素水平。结果:正常对照(A)组、DM性ED胰岛素(D)组、DM性ED联用(E)组、STZ(G)组睾酮(T)水平显著高于DM性ED对照(B)组、DM性ED伊木萨克(C)组、DM(F)组,有显著性差异(P0.01);正常对照(A)组、STZ(G)组促黄体生成激素(LH)水平显著低于DM性ED伊木萨克(C)组、DM性ED联用(E)组,有显著性差异(P0.05、P0.01);DM性ED对照(B)组、DM性ED补甫克比日丸(C)组促卵泡刺激素(FSH)水平显著低于DM性ED胰岛素(D)组、DM性ED联用(E)组,有显著性差异(P0.01、P0.05)。结论:维药罗补甫克比日丸可显著改善DM性ED大鼠睾酮水平,且与胰岛素联用优于单用,维药罗补甫克比日丸治疗DM性ED的作用机制可能与T、LH、FSH含量变化有关。     

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) was applied for the analysis of complex metabolite profiles from mouse spleen. The resulting two-dimensional chromatograms proved that mass spectral quality and sensitivity were largely improved by the enhanced resolution and zone compression, which are features of GC × GC operation, when compared to classical one-dimensional GC-TOF methods. The improved peak capacity of GC × GC allowed for peaks to be detected that could previously not be separated in one-dimensional GC. A measure of the combined power of chromatographic and mass spectral deconvolution resolution is called “analytical purity”, with higher values indicating less pure peaks. GC × GC-TOF lead to the detection of 1200 compounds with purity better than 0.2, compared to 500 compounds with purity up to 2.5 in one-dimensional GC-TOF. The compounds identified include many of the compounds previously reported in NMR studies and other methods on mammalian tissues. Spleen samples of several obese NZO mice and lean C57BL/6 control strains were analyzed in order to demonstrate the applicability of GC × GC-TOF for biomarker identification.This revised version was published online in June 2005. The previous version did not contain colour images.     

基于WOS和CNKI数据库分析肠道菌群与糖尿病的国内外研究趋势

目的 以文献计量学原理分析肠道菌群与糖尿病的研究现状和发展趋势。 方法 检索截至2019年12月31日的Web of Science外文数据库(WOS)和中国知网数据库(CNKI)内肠道菌群与糖尿病的所有研究文献,运用数据库提供的分析功能和Cite Space软件进行统计分析。 结果 WOS数据库内收录文献量以指数形式逐年上升。WOS数据库收录的文献被引95 466次,法国学者Cani为核心作者,学科类别以内分泌代谢学为主;中国作者文献被引10 061次,华大基因Wang Jun为国内领军人物,学科类别以食品科技学和内分泌腺及全身性疾病为主。WOS数据库中     

马齿苋不同部位提取物改善2型糖尿病大鼠糖脂代谢紊乱的比较研究

目的观察马齿苋及其不同提取部位对改善2型糖尿病大鼠胰岛素抵抗糖脂代谢紊乱的影响。方法应用小剂量链脲佐菌素加高热量饲养的方法建立实验性2型糖尿病大鼠模型,随机分为模型组、马齿苋组、马齿苋MH部位组、马齿苋MS部位组及多烯康对照组,并设正常对照组,各组大鼠相应地给与灌胃治疗12周;检测各组糖代谢及脂代谢血生化指标。结果糖代谢方面,马齿苋组能明显改善实验性2型糖尿病大鼠糖耐量异常,FINS明显低于模型组,相应地ISI显著提高;马齿苋MH部位具有改善实验性2型糖尿病大鼠糖耐量异常的趋势,FINS水平有所下降,ISI有所增加,与模型组比较接近统计学意义;而马齿苋MS部位对2型糖尿病大鼠糖耐量异常影响不大,改善胰岛素作用不明显。脂代谢方面,马齿苋组与模型组比较,显著升高血清HDL-C水平,同时降低血清TC、TG和FFA水平。马齿苋MH部位与模型组比较,显著降低血清TG水平,同时降低血清TC和FFA水平,但升高血清HDL-C水平不明显。马齿苋MS部位与模型组比较,显著降低血清FFA水平,降低血清TG接近统计学意义,但对血清TC和HDL-C水平无明显影响。结论马齿苋能明显改善2型糖尿病大鼠胰岛素抵抗糖代谢异常。马齿苋MH部位具有改善糖代谢的趋势,而马齿苋MS部位对糖代谢的影响不明显。马齿苋及其马齿苋MH部位、马齿苋MS部位对2型糖尿病大鼠胰岛素抵抗脂代谢异常均有明显的改善作用,但其侧重点各有不同,可能与其作用环节和机制不同有关。     

达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响

目的:探讨达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2(GLUT2)和葡萄糖转运蛋白4(GLUT4)基因表达的影响.方法:使用高脂饲料和一次性注射40 mg/kg链脲佐菌素(STZ)建立2型糖尿病大鼠模型,造模大鼠以空腹血糖(FBG)含量≥16.7 mmol/L时视为造模成功.造模成功后随机分为模型组(B组,生理盐水)...     

Visfatin、IL-6、TNF-α与2型糖尿病的相关研究

目的：探讨血浆visfatin、IL-6、TNF-α与2型糖尿病的关系。方法：2型糖尿病患者60例,正常对照组30例。根据体重指数分为肥胖组和非肥胖组。检测空腹血浆胰岛素、糖化血红蛋白、血糖、血脂、血压、visfatin、TNF-α、白介素-6等。计算体重指数、腰臀比值及稳态模型胰岛素抵抗指数（HOMA-IR）。结果：2型糖尿病组血浆visfatin、IL-6、TNF-α水平显著高于正常对照组（P〈0.05）;2型糖尿病组与正常肥胖组比较,糖尿病非肥胖组visfatin（301.60±58.07）明显升高,糖尿病肥胖组visfatin（336.68±37.61）、TNF-α（3.58±1.10）明显升高（P〈0.05）。多元线性相关分析表明,在肥胖的2型糖尿病患者中血浆TNF-α与糖化血红蛋白显著正相关,血浆IL-6与血糖（FPG）显著正相关,血浆visfatin与腰臀比值（WHR）显著正相关（P〈0.05）。结论：visfatin、IL-6、TNF-α的变化可能对2型糖尿病的发生、发展具有一定的作用。     

Effect of gliclazide on DNA damage in human peripheral blood lymphocytes and insulinoma mouse cells

Type 2 diabetes mellitus is associated with increased oxidative stress. Free radicals produced during this stress may damage various cellular components. Gliclazide, a second-generation sulfonylurea, is an oral hypoglycemic drug that possesses antioxidant properties. Therefore, gliclazide may diminish the harmful consequences of oxidative stress in diabetic patients. The aim of our study was to evaluate the action of gliclazide on DNA damage and repair in normal human peripheral blood lymphocytes and insulinoma mouse cells (beta-TC-6). DNA damage and repair were induced by hydrogen peroxide, gamma and ultraviolet radiation and MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) in the presence or absence of gliclazide and were analysed by the alkaline comet assay. DNA double-strand breaks were assayed by pulsed-field gel electrophoresis. Gliclazide protected DNA of both kinds of cells from DNA damage induced by chemicals and radiations. These results suggest that gliclazide may diminish the risk of free radical-related diseases associated with type 2 diabetes mellitus and possibly cancer.     

2型糖尿病早期大鼠外周神经节基因表达谱分析

糖尿病神经病变(Diabetic neuropathy,DN)是糖尿病在神经系统发生的多种并发病变的总称。文章旨在筛选2型糖尿病早期大鼠外周神经节差异表达的基因。采用Illumina大鼠基因表达芯片,比较糖尿病模型与非糖尿病大鼠外周神经节基因表达谱差异。结果表明,全基因组12 604个已知基因中,158个基因差异表达。糖尿病组与非糖尿病组相比,87个基因表达上调,71个表达下调。对差异表达的基因进行GO分析,发现上调基因所参与的最显著(P<0.001)的几个生物学过程都与神经细胞骨架及运动功能有关;下调基因所参与的最显著的生物学过程主要与"对病毒/生物刺激/其它生物的反应"有关。KEGG(Kyoto encyclopedia of genes and genomes)分析显示,差异表达的基因所参与的最显著(P<0.001)的生物学通路为代谢通路。结果表明:高血糖可导致糖尿病大鼠外周神经节代谢紊乱;高血糖可能通过免疫炎症反应、改变神经细胞骨架及运动功能相关的基因的表达,继而损害外周神经节的结构和功能。     

Pioglitazone reverses down-regulation of cardiac PPARgamma expression in Zucker diabetic fatty rats

Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARgamma in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARgamma agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARgamma, glucose transporter-4 and alpha-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARgamma, glut-4, and alpha-MHC expression levels in diabetic ZDF rats. Cardiac [(18)F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARgamma agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARgamma expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.     

Effect of coca-leaf chewing on salivary progesterone assays

Although there is evidence for reduced fertility in Andean and Himalayan populations at higher altitudes, factors other than hypoxia may be primarily responsible. A valuable approach in the investigation of these fertility determinants is the use of salivary steroid assays. However, coca-leaf chewing—a ubiquitous practice among high altitude Andean populations—has negative consequences for the accurate measurement of ovarian steroids. This report evaluates the effects of coca-leaf chewing on assays of salivary progesterone. Study participants include naive and habitual users of coca leaf from La Paz and El Alto, Bolivia. Approximately 300 saliva samples were collected immediately before, during, and after coca-leaf chewing. The series includes samples with and without the alkaloid enhancer typically used by coca-leaf chewers. Coca chewing produces false salivary progesterone values that mimic luteal phase values. On the basis of this study, an appropriate protocol is developed for the collection of salivary samples in coca-leaf chewing populations. These results verify the feasibility of salivary assays, even for very difficult field conditions, and highlight the necessity of establishing suitable collection procedures before full field implementation of saliva sampling. © 1993 Wiley-Liss, Inc.     

Alterations in beta-islets of Langerhans in alloxan-induced diabetic rats by marine Spirulina platensis

Marine Spirulina platensis may potentially influence the metabolic process in animal cells, and the effect of marine Spirulina platensis in normal and alloxan-induced diabetic rats was therefore investigated. Normal and diabetic rats (albino Wistar strain) were orally administered marine Spirulina platensis for 30 days and their blood levels of glucose and insulin and body weight changes were determined. Pancreatic histopathology was also noted. Treatment with marine Spirulina platensis caused significant alterations in the content of these indicators and therefore in the antidiabetic capacity of the treated animals compared to control rats.     

2型糖尿病大鼠模型的肾脏和动脉血管并发症

目的制备发病过程类似人类2型糖尿病的动物模型,并观察其肾脏和主动脉的病变特点。方法8周龄SD大鼠高脂、高糖饮食一个月后给予小剂量STZ腹腔注射建立2型糖尿病模型,于成模后4周及8周观察血管功能指标和肾脏功能指标,并对肾脏和血管的病理改变进行观察。结果模型组于成模后4周及8周出现高血糖、高血脂、胰岛素抵抗、肾功能改变和血管功能改变。肾脏光镜下见肾小球内皮及系膜细胞增生;肾小管水肿,管腔内有大量蛋白管型和细胞管型;肾盂区有大量淋巴细胞浸润。动脉血管电镜下见内皮细胞局部损伤严重;内皮细胞与内弹力板连接处空隙增加等。结论用高脂高糖饮食加小剂量STZ腹腔注射可成功制备2型糖尿病大鼠模型,成模后4周及8周后观察肾脏及大血管相继出现病变,是2型糖尿病血管病变研究的理想模型。