Time-Related Behaviour of Endocrine Secretion: Circannual Variations of FT3, Cortisol, Hgh and Serum Basal Insulin in Healthy Subjects

Four healthy young male volunteers were submitted to the study of circadian and circannual bioperiodicities of several hormones: FT3, FT4, Cortisol, HGH, prolactin, PTh and plasma insulin levels. They were observed for a whole year and their blood samples were collected six times a day, every other month. The results were analyzed by two-way ANOVA macroscopic analysis and Student r-test. Our data registered a circannual variation in the mean circadian plasma levels of the following hormones: Cortisol (peak in December), HGH (peak in April), FT3 (peak in April), insulin (peak in February). FT4, prolactin and PTH showed no cyclic variation during the period of observation.     

Circannual Rhythm of Insulin Release and Hypoglycemic Effect of Tolbutamide Stimulus in Healthy Man

Four healthy non obese young volunteers were observed for a 24-hr period, every other month, over the course of one year. Tolbutamide was injected i.v. each day of the experiment every four hours. Tolbutamide-induced insulin secretion (T.I.I.S.) was evaluated by planimetrically measuring insulin areas above basal levels. Tolbutamide-induced hypoglycemic effect was evaluated by measuring the blood glucose difference between the Sth and 25th minute after the drug injection (δG 5′-25′). The macroscopic evaluation of T.I.I.S. and δG 5′-2S′(mean chronograms) permitted the detection of the existence of a circannual variation of both variables. In particular the maximum level of the blood glucose drop (δG 5-25) was registered in February.

Subsequently the quantification of the rhythm of T.I.I.S. was obtained by fitting a sine curve, according to the Cosinor method. The highest insulin release was confirmed in winter.

As previously documented, the existence of a statistically significant circadian rhythm of T.I.I.S. was confirmed in the morning, i.e. the same period of the day in which insulin-induced hypoglycemia occurs.     

Circannual and Circa-Hemiannual Rhythms of Basal and Stimulated Gastric Secretion in Conscious Cats

Conscious cats equipped with a gastric fistula and a denervated Heidenhain pouch were submitted to weekly measurements of the basal and pentagastrin-stimulated gastric secretion for 1 to 14 years. Rhythms of basal secretion were documented in 37 cats for the group studies, in 25 cats only for the individual studies which required at least whole year data. Twelve-month or 6-month rhythms were detected for each variable studied, i.e. volume, acid, pepsin, fucose and uronic acid outputs in the group studies, with peaks for volume, acid and pepsin in Winter, peaks for uronic acid in Spring and Fall indicating different rhythms for oxyntic, chief and mucous cells. Individual studies detected rhythms in 25% of the analyses, and demonstrated male and female and cat to cat differences. Spectral analysis in 3 cats confirmed the differences in the individual rhythms with prominent peaks differing from 365 days in 50% of the cases. Chronopharmacological responses to pentagastrin were documented for volume, acid and pepsin outputs in 5 male and 6 female cats. Group analysis detected a Winter acrophase for volume and acid secretion and a Summer acrophase for pepsin secretion. Analysis of the stimulated response data showed interindividual variation but a higher percentage of detection for rhythms, i.e. 38% for all variables and 50% for pepsin secretion. Different rhythms in acid and pepsin secretion documented in individual studies could provide the basis of a better understanding of the discrepancies reported in the literature concerning the seasonal incidence of peptic ulcer disease.     

Circannual and Circa-Hemiannual Rhythms of Basal and Stimulated Gastric Secretion in Conscious Cats

Conscious cats equipped with a gastric fistula and a denervated Heidenhain pouch were submitted to weekly measurements of the basal and pentagastrin-stimulated gastric secretion for 1 to 14 years. Rhythms of basal secretion were documented in 37 cats for the group studies, in 25 cats only for the individual studies which required at least whole year data. Twelve-month or 6-month rhythms were detected for each variable studied, i.e. volume, acid, pepsin, fucose and uronic acid outputs in the group studies, with peaks for volume, acid and pepsin in Winter, peaks for uronic acid in Spring and Fall indicating different rhythms for oxyntic, chief and mucous cells. Individual studies detected rhythms in 25% of the analyses, and demonstrated male and female and cat to cat differences. Spectral analysis in 3 cats confirmed the differences in the individual rhythms with prominent peaks differing from 365 days in 50% of the cases. Chronopharmacological responses to pentagastrin were documented for volume, acid and pepsin outputs in 5 male and 6 female cats. Group analysis detected a Winter acrophase for volume and acid secretion and a Summer acrophase for pepsin secretion. Analysis of the stimulated response data showed interindividual variation but a higher percentage of detection for rhythms, i.e. 38% for all variables and 50% for pepsin secretion. Different rhythms in acid and pepsin secretion documented in individual studies could provide the basis of a better understanding of the discrepancies reported in the literature concerning the seasonal incidence of peptic ulcer disease.     

沉默长链非编码RNA Meg3损伤小鼠胰岛细胞的胰岛素分泌功能

MEG3是一种长链非编码RNA。已有研究证明,鼠源Meg3参与小鼠诱导多能干细胞、神经元和视网膜的分化过程。最新报道,MEG3在人胰岛β细胞中高表达,但其对维持成年胰岛β细胞的功能尚不清楚。本研究旨在探讨Meg3在小鼠胰岛细胞胰岛素分泌功能中的作用。实时定量PCR揭示,与Balb/c小鼠心、肝、脾、肺、肌、肾等组织/器官比较,Meg3在胰腺组织中高表达。在非糖尿病小鼠发生自发性糖尿病的第8、12周,Meg3在胰岛中的表达水平分别下调24%±8%和29%±9% (P<0.01);而当血糖升高20 mmol/L,小鼠胰岛中Meg3表达下调72%±16%(P<0.01)。在MIN6细胞中采用RNA干扰敲减Meg3的表达,在高糖浓度（20 mmol/L）刺激条件下,胰岛素分泌显著减少。小鼠静脉注射siRNA,结合血糖测定或葡萄糖耐受试验（IPGTT）显示,si-Meg3小鼠血清胰岛素水平显著下降。注射葡萄糖前血糖升高,注射葡萄糖后耐受能力降低;免疫组化分析显示,si-Meg3小鼠胰岛素阳性细胞的面积减少。实验结果提示,Meg3通过参与胰岛素的合成和分泌维持成年小鼠胰岛功能。Meg3表达失调可能参与I型糖尿病（T1DM）发病过程。     

Circadian and Seasonal Variations of Plasma Insulin and Cortisol Concentrations in the Syrian Hamster, Mesocricetus Auratus

Circadian rhythms of plasma insulin, Cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of Cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths.

The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores.     

Circulating Insulin Concentrations,Smoking, and Alcohol Intake Are Important Independent Predictors of Leptin in Young Healthy Men

Objective : Leptin, an adipocyte-secreted hormone, has been shown to signal the status of energy stores to the brain, regulate energy homeostasis, and mediate the neuroendocrine response to food deprivation. Obesity is associated with increased leptin levels, and several hormones, including insulin and glucocorticoids, have been associated with leptin levels and expression in rodents. Although obesity has been strongly associated with increased leptin in humans, a significant percentage of leptin's variability remains unexplained. The role of endogenous hormones, demographic factors, or certain life-style factors in explaining the residual variability of leptin levels has not yet been clarified. We performed this cross-sectional study to document the relative importance of obesity, lifestyle factor, and endogenous hormones in determining serum leptin levels. Research Methods and Procedures : We measured serum concentrations of insulin, Cortisol, testosterone, growth hormone, and dehydroepiandrosterone sulfate; ascertained anthropometric, demographic, and lifestyle characteristics; and studied these variables in relationship to serum leptin concentrations in a sample of young healthy men. Results : Obesity and alcohol intake were independently and positively associated with circulating leptin concentrations. Additionally, cigarette smoking was negatively and independently associated with leptin concentrations. Finally, serum insulin concentration was an independent hormonal determinant of circulating leptin concentrations, whereas serum testosterone was negatively associated with leptin only by bivariate analysis. Discussion : We conclude that, in addition to obesity, cigarette smoking, alcohol intake, and serum insulin levels are associated with leptin levels in a population of healthy young men.     

Insulin Secretion, DNA Damage, and Apoptosis in Human and Rat Islets of Langerhans Following Exposure to Nitric Oxide, Peroxynitrite, and Cytokines

Cytokine-induced damage may contribute to destruction of insulin-secreting beta-cells in islets of Langerhans during autoimmune diabetes. There is considerable controversy (i) whether human and rat islets respond differently to cytokines, (ii) the extent to which cytokine damage is mediated by induction of nitric oxide formation, and (iii) whether the effects of nitric oxide on islets can be distinguished from those of reactive oxygen species or peroxynitrite. We have analyzed rat and human islet responses in parallel, 48 h after exposure to the nitric oxide donor S-nitrosoglutathione, the mixed donor 3-morpholinosydnonimine, hypoxanthine/xanthine oxidase, peroxynitrite, and combined cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma). Insulin secretory response to glucose, insulin content, DNA strand breakage, and early-to-late stage apoptosis were recorded in each experiment. Rat islet insulin secretion was reduced by S-nitrosoglutathione or combined cytokines, but unexpectedly increased by peroxynitrite or hypoxanthine/xanthine oxidase. Effects on human islet insulin secretion were small; cytokines and S-nitrosoglutathione decreased insulin content. Both rat and human islets showed significant and similar levels of DNA damage following all treatments. Apoptosis in neonatal rat islets was increased by every treatment, but was at a low rate in adult rat or human islets and only achieved significance with cytokine treatment of human islets. All cytokine responses were blocked by an arginine analogue. We conclude: (i) Reactive oxygen species increased and nitric oxide decreased insulin secretory responsiveness in rat islets. (ii) Species differences lie mainly in responses to cytokines, applied at a lower dose and shorter time than in most studies of human islets. (iii) Cytokine effects were nitric oxide driven; neither reactive oxygen species nor peroxynitrite reproduced cytokine effects. (iv) Rat and human islets showed equal susceptibility to DNA damage. (v) Apoptosis was not the preferred death pathway in adult islets. (vi) We have found no evidence of human donor variation in the pattern of response to these treatments.     

Circadian Rhythm of Gastric Acid Secretion in Active Duodenal Ulcer: Chronobiological Statistical Characteristics and Comparison of Acid Secretory and Plasma Gastrin Patterns with Healthy Subjects and Post-Vagotomy and Pyloroplasty Patients

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p < 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p=0.034) circadian rhythm in unstimulated acid secretion in a group (N=14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N=17) of post-vagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.     

特发性矮小症患儿治疗前后血清IGF-1、IGFBP-3、25（OH）D、皮质醇水平变化及其与体格发育和骨龄的相关性分析

摘要 目的：探究特发性矮小症（ISS）患儿治疗前后血清胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）、25羟维生素D[25（OH）D]、皮质醇水平变化及其与体格发育和骨龄的相关性。方法：选取安徽省儿童医院于2017年7月～2021年3月收治的88例ISS患儿作为研究组。另选取同期体检健康儿童88例作为对照组。比较两组血清IGF-1、IGFBP-3、25（OH）D及皮质醇水平。比较ISS患儿治疗前后血清IGF-1、IGFBP-3、25（OH）D及皮质醇水平,体格指标以及骨龄指标。通过Pearson相关性分析ISS患儿血清IGF-1、IGFBP-3、25（OH）D及皮质醇水平与体格指标、骨龄指标的相关性。结果：研究组患儿血清IGF-1、IGFBP-3、25（OH）D水平均低于对照组,而皮质醇水平高于对照组（均P＜0.05）。ISS患儿治疗后血清IGF-1、IGFBP-3、25（OH）D水平均高于治疗前,而皮质醇水平低于治疗前（均P＜0.05）。ISS患儿治疗后身高、体重、骨龄年龄差（BAD）、骨龄指数（BAI）以及体质指数（BMI）均高于治疗前（均P＜0.05）。经Pearson相关性分析发现：ISS患儿血清IGF-1、IGFBP-3、25（OH）D水平与身高、体重、BAD、BAI以及BMI均呈正相关;皮质醇与身高、体重、BAD、BAI以及BMI均呈负相关（均P＜0.05）。结论：ISS患儿血清IGF-1、IGFBP-3、25（OH）D水平异常降低,皮质醇水平升高,且上述四项指标均和身高、体重、BAD以及BAI有关。     

地塞米松和胰岛素调节猪脂肪细胞SOCS-3、OB、 GLUT4和PPARg 基因的表达

猪是研究糖尿病最理想的模型动物, 研究胰岛素和胰岛素抵抗是研究糖尿病的重要环节。为明确SOCS-3在胰岛素抵抗中的作用, 分别用100 nmol/L的胰岛素, 300 nmol/L的地塞米松处理原代培养的猪脂肪细胞诱导胰岛素抵抗; 利用半定量RT-PCR技术分别检测SOCS-3、OB、GLUT4和PPARg 基因表达变化。结果发现, 胰岛素增加了GLUT4、SOCS-3和PPARg 基因的表达, 对OB基因表达变化没有显著性影响; 地塞米松诱导的胰岛素抵抗状态下OB和SOCS-3基因表达水平升高, 而GLUT4和PPARγ基因表达水平显著下调。研究结果表明, GLUT4基因表达量水平的升高可能是由于PPARg的高表达引起, SOCS-3基因的不同表达水平对胰岛素信号的抑制效果不同。地塞米松诱导的胰岛素抵抗不仅表现在对葡萄糖转运的抑制, 也反映在抑制了胰岛素信号; 而SOCS-3基因可能是消除胰岛素抵抗的一个有效靶基因。     

氯化镧对牛血清谷胱甘肽过氧化物酶、生长激素、胰岛素、三碘甲腺原氨酸和四碘甲状腺原氨酸浓度的影响

选用36头平均体重420 kg,年龄2.5岁的中国西门答尔阉牛,采用随机区组设计分为4组,以混合精料和风干玉米秸秆为基础日粮,研究日粮中添加不同水平氯化镧对西门答尔阉牛营养物质消化、血清谷胱甘肽过氧化物酶、生长激素、胰岛素、三碘甲腺原氨酸和四碘甲状腺原氨酸浓度的影响。结果表明:实验至第60天时,每天添加0.9 g氯化镧的饲粮有机物质、粗蛋白、粗脂肪、粗纤维、中性洗涤纤维和酸性洗涤纤维的表观消化率较对照组和其它处理组分别提高了8.09%、7.13%、15.20%、9.47%、13.09%和20.48%,血清谷胱甘肽过氧化物酶活性较对照组和其它处理组显著提高了8.22、3.95和5.04个单位,血清生长激素、胰岛素浓度、三碘甲腺原氨酸和四碘甲状腺原氨酸浓度均显著高。     

2型糖尿病合并冠心病患者血清IL-6、PCT、CatS、Gal-3与糖脂代谢、胰岛素抵抗和心功能的相关性分析

摘要 目的：探讨2型糖尿病（T2DM）合并冠心病患者血清白介素-6（IL-6）、降钙素原（PCT）、组织蛋白酶S（CatS）、半乳糖凝集素3（Gal-3）与糖脂代谢、胰岛素抵抗和心功能的相关性。方法：选择我院2019年2月～2021年2月收治的102例T2DM患者,将其根据是否伴有冠心病分成单纯T2DM组（n=62）和T2DM合并冠心病组（n=40）。另取同期健康体检人员50例作为对照组。比较三组血清IL-6、PCT、CatS、Gal-3水平。对比单纯T2DM组与T2DM合并冠心病组间糖脂代谢、胰岛素抵抗和心功能指标差异,并分析血清IL-6、PCT、CatS、Gal-3与上述指标的相关性。结果：单纯T2DM组、T2DM合并冠心病组的血清IL-6、PCT、CatS、Gal-3水平均高于对照组,且T2DM合并冠心病组上述各项指标水平均高于单纯T2DM组（P＜0.05）。T2DM合并冠心病组空腹血糖（FPG）、低密度脂蛋白胆固醇（LDL-C）水平以及胰岛素抵抗指数（HOMA-IR）均高于单纯T2DM组（P＜0.05）,而两组间餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、空腹胰岛素（FINS）水平比较无统计学差异（P>0.05）。T2DM合并冠心病组左心室射血分数（LVEF）、左心室收缩末期容积（LVESV）及左心室舒张末期容积（LVEDV）均低于单纯T2DM组（P＜0.05）。Pearson相关性分析结果显示：T2DM合并冠心病患者的血清IL-6、PCT、CatS、Gal-3水平与LDL-C水平、HOMA-IR均呈正相关,而与LVEF、LVESV、LVEDV均呈负相关（P＜0.05）。结论：T2DM合并冠心病患者血清IL-6、PCT、CatS、Gal-3水平呈异常高表达,且和糖脂代谢、胰岛素抵抗和心功能密切相关,对患者病情具有一定辅助评估价值。     

血清CREB、FoxO1、NLRP3与妊娠期糖尿病患者胰岛素抵抗的相关性分析及对妊娠结局的影响

摘要 目的：探讨血清环磷腺苷效应元件结合蛋白（CREB）、叉头框蛋白O1（FoxO1）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）与妊娠期糖尿病（GDM）患者胰岛素抵抗（IR）的相关性分析及对妊娠结局的影响。方法：选取2019年12月～2022年8月邵阳学院附属第一医院收治的136例GDM患者为GDM组,根据妊娠结局分为结局不良组（42例）和结局良好组（94例）,另选取55名健康孕妇为对照组。收集GDM患者临床资料,检测血清CREB、FoxO1、NLRP3水平并计算稳态模型评估-胰岛素抵抗（HOMA-IR）。采用Pearson相关性分析GDM患者血清CREB、FoxO1、NLRP3水平与HOMA-IR的相关性,多因素Logistic回归分析GDM患者妊娠结局不良的影响因素,受试者工作特征（ROC）曲线分析血清CREB、FoxO1、NLRP3水平对GDM患者妊娠结局不良的预测价值。结果：与对照组比较,GDM组血清CREB、FoxO1、NLRP3水平和HOMA-IR升高（P＜0.05）。Pearson相关性分析显示,GDM患者血清CREB、FoxO1、NLRP3水平与HOMA-IR呈正相关（P均＜0.001）。136例GDM患者妊娠结局不良发生率为30.88%。多因素Logistic回归分析显示,HOMA-IR、CREB、FoxO1、NLRP3升高为GDM患者妊娠结局不良的危险因素（P＜0.05）。ROC曲线分析显示,血清CREB、FoxO1、NLRP3水平联合预测GDM患者妊娠结局不良的曲线下面积大于CREB、FoxO1、NLRP3单独预测。结论：血清CREB、FoxO1、NLRP3水平升高与GDM患者IR和妊娠结局不良密切相关,可能成为GDM患者妊娠结局不良的辅助预测指标。     

经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清MMP-3、TIMP-1、IL-6及疗效的影响

目的:探讨经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶抑制因子-1(TIMP-1)、白细胞介素-6(IL-6)及疗效的影响。方法:选择60例2016年10月到2017年3月我院接诊的老年骨质疏松性胸腰椎压缩骨折患者,依照随机数表法分为实验组和对照组,每组30例,在都给予常规药物治疗的基础上,对照组给予复位枕垫和康复训练治疗,实验组采用经皮椎体成形术治疗。结果:治疗前,两组血清MMP-3、TIMP-1、IL-6水平无差异(P0.05);治疗后,两组血清MMP-3、IL-6水平均降低,实验组下降幅度更大,两组血清TIMP-1水平均升高,实验组上升幅度更大(P0.05);治疗前,两组患者VAS评分无差异(P0.05),治疗1周及治疗后,实验组患者VAS评分均低于对照组(P0.05);治疗前,两组患者Cobb角无差异(P0.05),治疗后,两组患者Cobb均明显下降,实验组较对照组下降更大(P0.05);治疗前,两组患者伤椎高度比无差异(P0.05),治疗后,两组伤椎高度比明显下降,实验组低于对照组(P0.05);治疗后,实验组有效率96.67%大于对照组的76.67%,差异显著(P0.05)。结论:经皮椎体成形术能有效降低患者血清MMP-3、IL-6水平,恢复TIMP-1水平,能显著提高治疗老年骨质疏松性胸腰椎压缩骨折的疗效     

肥胖合并高脂血症患者血清食欲素A、25-羟维生素D3、瘦素水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性分析

摘要 目的：探讨肥胖合并高脂血症患者血清食欲素A（orexin A）、25-羟维生素D3[25-(OH)D3]、瘦素（Leptin）水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性。方法：选择2019年2月至2021年12月中国医科大学附属第四医院收治的105例肥胖合并高脂血症患者为研究组,另取同期在中国医科大学附属第四医院健康体检的73例志愿者为对照组。检测并对比两组血清orexin A、25-(OH)D3、Leptin、胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标水平的差异。采用Pearson相关性分析血清orexin A、25-(OH)D3、Leptin水平与胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标的相关性。结果：研究组血清orexin A、25-(OH)D3水平低于对照组,而Leptin水平高于对照组（P＜0.05）。研究组空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）水平均高于对照组（P＜0.05）。研究组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平高于对照组,而高密度脂蛋白胆固醇（HDL-C）水平低于对照组（P＜0.05）。研究组体质量指数（BMI）、腰臀比、腰高比均高于对照组（P＜0.05）。肥胖合并高脂血症患者的血清orexin A、25-(OH)D3水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈负相关,与HDL-C水平呈正相关（P＜0.05）;Leptin水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈正相关,与HDL-C水平呈负相关（P＜0.05）。结论：肥胖合并高脂血症患者血清orexin A、25-(OH)D3水平降低,Leptin水平升高,且与胰岛素抵抗、脂代谢紊乱及肥胖指标升高有关。     

Serum Estradiol 17β, Progesterone,and Relative Luteinizing Hormone Levels in Saimiri sciureus: Cyclic Variations and the Effect of Laparoscopy and Follicular Aspiration

With increasing use of the squirrel monkey (Saimiri sciureus) in reproductive studies, a precise knowledge of the hormonal variations within the cycle becomes essential for timing of ovulation. The frequent utilization of laparoscopy for follicle aspiration and oocyte recovery warrants analysis of hormonal alterations.     

The Full-Length, Cytoplasmic C-Terminus of the β2-Adrenergic Receptor Expressed in E. coli Acts as a Substrate for Phosphorylation by Protein Kinase A, Insulin Receptor Tyrosine Kinase, GRK2, but Not Protein Kinase C and Suppresses Desensitization when Expressed in Vivo

The ability of the cytoplasmic, full-length C-terminus of the β2-adrenergic receptor (BAC1) expressed in Escherichia coli to act as a functional domain and substrate for protein phosphorylation was tested. BAC1 was expressed at high-levels, purified, and examined in solution as a substrate for protein phosphorylation. The mobility of BAC1 on SDS–PAGE mimics that of the native receptor itself, displaying decreased mobility upon chemical reduction of disulfide bonds. Importantly, the C-terminal, cytoplasmic domain of the receptor expressed in E. coli was determined to be a substrate for phosphorylation by several candidate protein kinases known to regulate G-protein-linked receptors. Mapping was performed by proteolytic degradation and matrix-assisted laser desorption ionization, time-of-flight mass spectrometry. Purified BAC1 is phosphorylated readily by protein kinase A, the phosphorylation occurring within the predicted motif RRSSSK. The kinetic properties of the phosphorylation by protein kinase A displayed cooperative character. The activated insulin receptor tyrosine kinase, which phosphorylates the beta-adrenergic receptor in vivo, phosphorylates BAC1. The Y364 residue of BAC1 was predominantly phosphorylated by the insulin receptor kinase. GRK2 catalyzed modest phosphorylation of BAC1. Phosphorylation of the human analog of BAC1 in which Cys341 and Cys378 were mutated to minimize disulfide bonding constraints, displayed robust phosphorylation following thermal activation, suggesting under standard conditions that the population of BAC1 molecules capable of assuming the “activated” conformer required by GRKs is low. BAC1 was not a substrate for protein kinase C, suggesting that the canonical site in the second cytoplasmic loop of the intact receptor is preferred. The functional nature of BAC1 was tested additionally by expression of BAC1 protein in human epidermoid carcinoma A431 cells. BAC1 was found to act as a dominant-negative, blocking agonist-induced desensitization of the beta-adrenergic receptor when expressed in mammalian cells. Thus, the C-terminal, cytoplasmic tail of this G-protein-linked receptor expressed in E. coli acts as a functional domain, displaying fidelity with regard to protein kinase action in vivo and acting as a dominant-negative with respect to agonist-induced desensitization.     

Cytokinins: Synthesis of 2-, 8-, and 2,8-substituted 6-(3-methyl-2-butenylamino)purines and their relative activities in promoting cell growth

We have synthesized 2- and 8-monosubstituted and 2,8-disubstituted derivatives of the cytokinin 6-(3-methyl-2-butenylamino)purine (N⁶-isopentenyladenine) and have shown the dependence of growth-promoting activity in the tobacco bioassay upon the position, number, and type of substituent. The representative substituent groups were MeS, Me, MeSO₂, C₆H₅CH₂S, HS and Cl. The 8-methyl derivative was exceptional in being more active than the unsubstituted parent compound. In general, substitution in the 8-position decreases activity less than substitution in the 2-position, with the exception of the electron-attracting methylsulfonyl. Substitution in both the 2- and 8-positions lowers the activity more than substitution at either single position on the adenine nucleus, with the exception of the 2,8-dimethyl derivative. The chloro and methylthio derivatives show activity in the same range as the methyl derivatives, and the mercapto compounds, which exist mainly as CS tautomers, show somewhat less activity than the corresponding methylthio compounds. Bulky (C₆H₅CH₂S and MeSO₂) and strongly electron-attracting (MeSO₂) substituents cause relatively great reduction in cytokinin activity.