Background: Circadian locomotor output cycles kaput protein (CLOCK) plays a crucial role in glucose homeostasis and controlling insulin secretion. However, the mechanism of the CLOCK regulating rhythmic insulin secretion has not been fully understood. Methods: Rhythmic expression of the CLOCK in rat pancreatic beta cell was detected. INS-1 cells were transfected with siRNAs to knockdown the CLOCK before the cells were incubated with different concentrations of glucose. Insulin secretion was analyzed by ELISA method. Expression of the L-type calcium channel protein (Cav1.2, Cacnalc) was determined both in the CLOCK-knockdown cells and the control cells. Calcium influx was probed by fluorescent. Chromatin immunoprecipitation (ChIP) test and dualluciferase reporter gene experiments were applied to verify the relationship between the CLOCK and Cav1.2. Results: The CLOCK is abundantly expressed in rat pancreatic beta cells. Transcription level of the CLOCK showed rhythmicity in the beta cells. Compared to the control group, insulin release was significantly impaired with 25 mM glucose incubation in the CLOCK-knockdown group, but not showed with 2.5 mM glucose incubation. The expression of Cav1.2 and the influx of calcium were significantly decreased in the CLOCK-knockdown group with 25 mM glucose incubation. ChIP test indicted that the CLOCK bound to 444 454 region of the Cacnalc promoter of the INS-1 cells, but the binding was significantly reduced following the CLOCK-knockdown. Luciferase experiment was in accordance with the finding of ChIP. Conclusions: The CLOCK mediating Cav(1.2) expression may point out a potential pathway of circadian rhythm affecting insulin secretion. (C) 2021 Elsevier Inc. All rights reserved.

Background Canagliflozin (CANA) and metformin (MET) can both be used in the treatment of type 2 diabetes (T2DM) , but the clinical efficacy of combined use remains to be further clarified. Objective To elevate the efficacy and safety of CANA combined with MET in the treatment of T2DM, and to provide clinical reference for the treatment of T2DM. Methods A systematic review of published randomized controlled trials (RCTs) of 100 mg and/or 300 mg CANA combined with MET for T2DM performed in PubMed, Cochrane Library, EMBase, Clinical Trials.gov, CNKI Database, VIP Database, Wanfang Databases from inception to 18 April 2021 were retrieved by computer, and the included references were retrieved manually. After literature screening, data extraction and quality evaluation, meta-analysis was performed using RevMan 5.3 software. Results A total of 9 RCTs with 6 224 patients were included. Meta-analysis results showed that the levels of glycosylated hemoglobin (HbA1c) , fasting blood glucose (FPG) , body weight, systolic blood pressure (SBP) , diastolic blood pressure (DBP) , and triacylglycerol (TG) in the 100 mg CANA combined with MET group and the 300 mg CANA combined with MET group were lower than placebo control group (P<0.05) . The levels of pancreatic β-cell function index (HOMA-β) , low-density lipoprotein cholesterol (LDL-C) , and high-density lipoprotein cholesterol (HDL-C) in the 100 mg CANA combined with MET group were higher than those in the placebo control group (P<0.05) . The levels of HbA1c and SBP in the 300 mg CANA combined with MET group were lower than those in the active control group, and the level of HOMA-β was higher than that in the active control group (P<0.05) . The FPG, body weight, DBP and TG in the 100 mg CANA combined with MET group and 300 mg CANA combined with MET group were lower than those in the active control group, and the levels of LDL-C and HDL-C were higher than those in the active control group (P<0.05) . The incidence of reproductive system infection (female) in the 100 mg CANA combined with MET group was higher than that in the placebo control group (P<0.05) . The incidence of reproductive system infection (female) and osmotic diuresis-related adverse events in the 300 mg CANA combined with MET group was higher than that in the placebo control group (P<0.05) . The incidence of reproductive system infection (male) , reproductive system infection (female) , and osmotic diuresis in the 100 mg CANA combined with MET group and 300 mg CANA combined with MET group was higher than that in the active control group (P<0.05) . Conclusion 100 mg and 300 mg of CANA combined with MET can effectively reduce HbA1c and FPG levels, body weight, blood pressure and TG levels, and increase LDL-C and HDL-C levels in T2DM patients. For patients with T2DM poorly controlled by MET, it may be considered in combination with CANA, but attention should be paid to infection of the reproductive system. Therefore, high-quality large-sample trials are still needed to confirm the long-term safety of different doses of CANA combined with MET.

Both poor sleep and diabetic kidney disease are closely associated with inflammation. However, the correlation between poor sleep and diabetic kidney disease has not been well clarified. Thus, the aim of this study was to determine the mediating role that inflammatory markers play in the pathogenic effect of poor sleep on the severity of diabetic kidney disease (DKD). A cross-sectional survey was conducted on 336 patients with type 2 diabetes (T2D). DKD was diagnosed according to the guidelines of the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (NKF-K/DOQI). The Pittsburg Sleep Quality Index (PSQI) score was applied to assess patients for the quality of their sleep. Patients with a PSQI score of more than 5 were assigned to the poor sleep group, and the rest of the patients were assigned to the good sleep group. Circulating levels of six inflammatory biomarkers related to poor sleep and DKD were measured. The prevalence of DKD was higher in patients with poor sleep quality than in those with good sleep quality (42% vs. 25%, P = 0.002). After adjustment, poor sleep quality (PSQI score OR 1.075 [95%CI 1.018–1.135], P = 0.009) remained independently associated with DKD. PSQI score was found to be positively related to fibroblast growth factor (FGF23), interleukin 6 (IL-6), P-selectin, and intercellular adhesion molecule-1 (ICAM-1) (P < 0.01), rather than fibrinogen and C-reactive protein (CRP) in linear regression models. As revealed by multiple mediation analysis, FGF23 and IL-6 mediated 26% and 23% of the relationship between PSQI score and urinary microalbumin (UMA), respectively. Similarly, the FGF23 and ICAM-1, instead of IL-6 and P-selectin, mediated 32% and 24% of the association between PSQI and estimated glomerular filtration rate (eGFR), respectively. Poor sleep quality is independently associated with DKD. These results suggest that inflammatory markers contribute to a pathogenic connection between poor sleep and DKD.

目的:探讨利拉鲁肽对人胰岛淀粉样多肽聚集性及细胞毒性的影响.方法:采用硫磺素T荧光法检测淀粉样纤维聚集的动力学,采用透射电镜检测淀粉样纤维的形态.分离Wistar大鼠胰岛,采用简单随机化分组的方法将大鼠胰岛随机分配成空白对照组、人胰淀素组、人胰淀素+利拉鲁肽组.24 h后采用Annexin-V/PI荧光染色及逆转录聚合酶链反应检测细胞凋亡及炎性因子白细胞介素(IL)-1β、肿瘤坏死因子α(TNFα)、单核细胞趋化蛋白-1(CCL-2)mRNA的表达.结果:人胰淀素单独孵育时,荧光于1.6 h左右开始上升,并随时间延长逐渐增加,3.4 h后平稳,动力学曲线呈S型曲线;人胰淀素与利拉鲁肽(500 nmol/L)以10:1分子浓度共同孵育时,荧光信号上升延迟缓慢;以1:1分子浓度共同孵育时,荧光信号未见明显增加,动力学曲线呈直线型.透射电镜结果显示,人胰淀素单独孵育可见大量长条状纤维聚集,人胰淀素与利拉鲁肽(2μmol)以10:1浓度共同孵育后纤维数量明显减少,且短小模糊;1:1(20μmol利拉鲁肽)浓度共同孵育后,无法找到纤维结构.与空白对照组相比,人胰淀素组IL-1、TNFα、CCL-2基因的mRNA表达均增加,而人胰淀素+利拉鲁肽组表达均下降(F=429.68、48.79、153.39,均P<0.05).人胰淀素组细胞凋亡率与空白对照组相比明显升高;人胰淀素+利拉鲁肽组凋亡率比人胰淀素组降低(F=514.34、16.14、18.47,均P<0.05).结论:利拉鲁肽抑制胰淀素聚集,减少胰岛细胞炎症及凋亡.

目的 初步探究大鼠胰岛beta细胞截短型P糖蛋白(mini-P糖蛋白,65 kD)表达的存在.方法 采用实时荧光定量PCR(RT-qPCR)检测雄性Wistar大鼠胰岛、肝脏和INS-1细胞中P糖蛋白主要调控基因abcb1b N端、C端及abcb1a的表达情况.提取INS-1细胞的总RNA,设计abcb1b基因3'末端和5'末端引物,逆转录合成对应的cDNA,PCR产物经过地高辛-dUTP标记,获得Northern blot检测探针.提取大鼠胰岛总RNA,通过甲醛变性电泳分离RNA并转至尼龙膜,将探针与尼龙膜上RNA进行杂交,检测abcb1b基因的选择性剪切.提取INS-1细胞蛋白,分为蛋白酶抑制剂组(加入蛋白酶抑制剂)和无蛋白酶抑制剂组,利用Western blot技术检测截短型P糖蛋白的表达差异.结果 实时荧光定量PCR结果 显示大鼠胰岛、INS-1细胞及肝的abcb1b表达量远大于abcb1a,差异具有统计学意义(P<0.05).大鼠胰岛、INS-1细胞的abcb1b C端拷贝数大于N端(约1.7倍),差异具有统计学意义(P<0.05).Northern blot杂交结果 为单条带,分子量与全长P糖蛋白符合,未检测到abcb1b基因选择性剪切条带.Western blot结果 显示无蛋白酶抑制剂组仅有65 kD截短型P糖蛋白的表达,而蛋白酶抑制剂组主要表达分子量为170 kD的全长P糖蛋白,截短型P糖蛋白表达显著减低,与无蛋白酶抑制剂组相比,截短型P糖蛋白的表达差异具有统计学意义(P<0.05).结论 初步认为在大鼠胰岛beta细胞探测到的截短型P糖蛋白可能为蛋白降解产物,并非abcb1b基因选择性剪切的结果 .

Background Mobile-based interventions appear to be promising in ameliorating huge burdens experienced by patients with type 2 diabetes. However, it is unclear how effective mobile-based interventions are in glycemic management of patients with type 2 diabetes based on real-world evidence. Objective This study aimed to evaluate the effectiveness of a mobile-based intervention on glycemic control in patients with type 2 diabetes based on real-world population data. Methods This retrospective, propensity score-matched cohort study analyzed longitudinal data from a clinical electronic health database. The study population included 37,913 patients with type 2 diabetes at cohort entry between October 1, 2016, and July 31, 2018. A total of 2400 patients were matched 1:1, using propensity score matching, into the usual care and mobile health (mHealth) groups. The primary outcomes of glycemic control included control rates of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial 2-hour blood glucose (P2BG). Mean values and variation trends of difference with 95% CI were the secondary outcomes. The general linear model was used to calculate repeated-measures analyses of variance to examine the differences between the two groups. Subgroup and sensitivity analyses were performed. Results Of the 2400 patients included in the analysis, 1440 (60.00%) were male and the mean age was 52.24 years (SD 11.56). At baseline, the control rates of HbA1c, FBG, and P2BG in the mHealth and usual care groups were 45.75% versus 47.00% (P=.57), 38.03% versus 32.76% (P=.07), and 47.32% versus 47.89% (P=.83), respectively. At the 3-, 6-, 9-, and 12-month follow-ups, the mHealth group reported higher control rates of HbA1c than did the usual care group: 69.97% versus 46.06% (P<.001), 71.89% versus 61.24% (P=.004), 75.38% versus 53.44% (P<.001), and 72.31% versus 46.70% (P<.001), respectively. At the four follow-up sessions, the control rates of FBG in the mHealth and usual care groups were statistically different: 59.24% versus 34.21% (P<.001), 56.61% versus 35.14% (P<.001), 59.54% versus 34.99% (P<.001), and 59.77% versus 32.83% (P<.001), respectively. At the four follow-up sessions, the control rates of P2BG in the mHealth group were statistically higher than in the usual care group: 79.72% versus 48.75% (P<.001), 80.20% versus 57.45% (P<.001), 81.97% versus 54.07% (P<.001), and 76.19% versus 54.21% (P=.001), respectively. At the four follow-up sessions, the percentages of HbA1c reduction in the mHealth group were 8.66% (95% CI 6.69-10.63), 10.60% (95% CI 8.66-12.54), 10.64% (95% CI 8.70-12.58), and 8.11% (95% CI 6.08-10.14), respectively. At the four follow-up sessions, the percentages of P2BG reduction in the mHealth group were 8.44% (95% CI 7.41-10.73), 17.77% (95% CI 14.98-20.23), 16.23% (95% CI 13.05-19.35), and 16.91% (95% CI 13.17-19.84), respectively. Starting from the sixth month, the mean HbA1c and P2BG values in the two groups increased slightly. Conclusions This mobile-based intervention delivered by a multidisciplinary team can better improve glycemic control rates of patients with type 2 diabetes than usual care. These effects were best sustained within the first 6 months. Starting from the sixth month, intensive management needs to be conducted to maintain long-term effectiveness of the mobile-based intervention.

目的 探讨不同血糖控制水平的T2DM患者身体成分差异,并分析身体成分与血糖控制水平的相关性.方法 选取2015年7月至2016年7月天津医科大学代谢病医院448例T2DM患者行横断面研究,通过双能X射线吸收仪测定其身体成分.HbA1c≤7％为血糖控制佳组,HbA1c水平>7％为血糖控制不佳组,采用Spearman相关分析及多元线性回归分析血糖控制水平与身体成分的关系.结果 血糖控制不佳组总瘦体重、躯干瘦体重及四肢瘦体重低于血糖控制佳组[(47.46±7.75)vs(51.84±10.33)kg,(23.30±3.91)vs(25.47±5.00)kg,(24.13±3.81)vs(26.32±5.45)kg,P<0.01],脂肪含量及分布,差异无统计学意义(P>0.05).Spearman相关分析显示,内脏脂肪含量与HbA1c呈正相关(r=0.136,P<0.01).多元线性回归分析结果显示,内脏脂肪含量、总脂肪含量、总瘦体重含量、躯干及四肢瘦体重含量是HbA1c的影响因素.结论 T2DM患者血糖控制水平可能与瘦体重含量有关.

目的 初步探讨不同剂量他克莫司导致大鼠血糖升高的机制.方法 将20只SD大鼠随机分为低剂量组(0.1 mg/kg)、中剂量组(0.5 mg/kg)、高剂量组(1.0 mg/kg)、对照组4组,每组5只;前3组每日皮下注射相应剂量的他克莫司,连续注射1周,对照组给予等体积橄榄油.实验期间隔日监测动物体质量.药物干预1周后行腹腔注射葡萄糖耐量试验(2 g/kg),统计空腹血糖(FBG)、空腹胰岛素(FINS)和稳态模型下胰岛素抵抗指数(HOMA-IR).摘取大鼠胰体尾部制备病理组织切片,免疫组化染色测量胰岛β细胞面积,qPCR检测胰岛组织胰岛素分泌相关基因Epac、Rim2、Piccolo、Rab3a、Munck13的表达.结果 与对照组相比,他克莫司干预组体质量降低,中高剂量组的下降幅度大于低剂量组.不同剂量他克莫司干预组均出现糖耐量异常,中、高剂量组血糖水平和曲线下面积均较低剂量组升高,且呈剂量依赖性(P<0.05).实验期间4组间FBG、FINS和HOMA-IR比较差异无统计学意义(P>0.05).免疫组化染色结果显示中高剂量组β细胞数量较低剂量组与对照组减少(P<0.05),低剂量组与对照组差异无统计学意义(P>0.05).低剂量组胰岛素分泌相关蛋白Epac、Rim2、Piccolo、Rab3a、Munck13转录水平均较对照组下降(P<0.05).结论 在胰岛β细胞数量并未减少,且未出现胰岛素抵抗的情况下,小剂量他克莫司干预所引起的糖耐量异常与胰岛素分泌过程紊乱相关.

目的 探究生物钟节律紊乱对糖尿病肥胖小鼠(ob/ob)糖代谢及胰岛素分泌的影响.方法 选取同体重的6～8周龄C57BL/6及ob/ob小鼠各12只,随机分为对照组(C57组)、糖尿病组(OB组)、对照组+生物钟节律干扰组(C57+CSD组)、糖尿病组+生物钟节律干扰组(OB+CSD组),每组6只. C57+CSD组和OB+CSD组小鼠分别置于高台水环境下干扰其生物钟节律. C57组和OB组小鼠分别置于标准饲养笼中,其生物钟节律不受干扰,动物体重每天监测1次. 4周后行小鼠体内腹腔注射葡萄糖耐量实验(IPGTT,2 g/kg),分离实验小鼠胰岛行体外葡萄糖刺激胰岛素分泌实验(GSIS).结果 C57、C57+CSD和OB组体重分别增长22.92%、0.42%和26.16%,而OB+CSD组下降0.17%.空腹血糖测定显示:OB组与OB+CSD组血糖值水平高于C57组和C57+CSD组(P＜0.05);IPGTT实验显示:OB组小鼠血糖峰值明显后移,且在15、30、60、90 min的血糖均高于C57组(P＜0.05);C57+CSD组小鼠各时间点血糖均高于C57组(P＜0.05),OB+CSD组小鼠于120 min的血糖高于OB组(P＜0.05);体内、体外胰岛素测定显示:C57胰岛素分泌低于OB组(P＜0.05),C57+CSD组胰岛素分泌低于C57组(P＜0.05), OB+CSD组血清及体外胰岛胰岛素分泌低于OB组(P＜0.05).结论 生物钟节律是维护糖代谢稳态的重要环节,其紊乱可能导致正常及糖尿病小鼠胰岛素分泌的减低.

Aim: Circadian rhythm controls a wide variety of physiological processes in the body. Disruption of the circadian clock in metabolic tissues may increase the risk of diabetes, obesity, and metabolic syndrome. The following study investigated whether the expression of clock genes of peripheral blood cells is impaired in type 2 diabetes (DT2) and whether inflammatory markers are associated with circadian clock gene expression in DT2 patients. Materials and methods: Blood samples were obtained from 36 DT2 patients and 14 nondiabetic volunteers. Transcript levels of circadian clock genes were analyzed using real-time quantitative PCR; plasma inflammatory markers were measured by ELISA or clinical laboratory test. Results: The CLOCK, BMAL1, PER1, CRY1 and CRY2 mRNA levels were decreased in the diabetic patients. In addition, HbA1c levels were negatively correlated with BMAL1, PER1 and CRY1 mRNA levels. The levels of IL-6, TNF-alpha and CRP were higher in diabetic subjects compared to control subjects. Impaired expression of circadian clock gene was interrelated with the elevated levels of plasma IL-6 and TNF. Moreover, amultiple linear regression showed that plasma IL-6 level was correlated with impaired expression of circadian clock gene. Conclusions: Circadian clock genes are reduced in peripheral leucocytes of DT2 patients. Furthermore, impaired expression of circadian clock gene are interrelatedwith the elevated levels of plasma inflammatory markers. (C) 2019 Published by Elsevier B.V.

目的 分析甘精胰岛素联合诺和锐在2型糖尿病临床治疗中的实际应用效果.方法 选取我院2013年1月～2017年1月收治的160例2型糖尿病患者,采用抽签的方式将其分为对照组和观察组各80例.对照组患者采用诺和锐治疗,观察组患者在诺和锐治疗的基础上联合甘精胰岛素治疗,观察对比两组患者的血糖、血脂和血流变等指标.结果 观察组患者的血糖达标时间明显短于对照组,差异有统计学意义(P＜0.05),观察组患者的低血糖发生率明显低于对照组,差异有统计学意义(P＜0.05),观察组患者的空腹血糖水平和餐后2h血糖水平也明显低于对照组,差异有统计学意义(P＜0.05);治疗后两组患者的TG、TC指标均较治疗前有所降低,且观察组低于对照组,差异有统计学意义(P＜0.05);LDL-C和HDL-C指标治疗前后变化不明显,差异无统计学意义(P＞0.05);两组患者的血浆粘度、全血粘度和血小板黏附率指标均较治疗前有所降低,且观察组低于对照组,差异有统计学意义(P＜0.05).结论 在2型糖尿病的治疗过程中采用甘精胰岛素联合诺和锐可以更好的改善患者的各项指标,有利于缩短患者的血糖达标时间,降低低血糖的发生率,有效控制患者的血糖水平,这对于疾病的治疗具有积极的意义.

目的 探讨P-糖蛋白过表达对大鼠胰岛β细胞系INS-1细胞和大鼠胰岛β细胞分化的影响.方法 分别构建INS-1细胞(Ad-abcb1b腺病毒感染)和SD大鼠(Ins2-abcb1b随机插入)P-糖蛋白过表达模型.以阴性对照病毒和野生型SD大鼠为对照组,P-糖蛋白过表达组和转基因SD大鼠为实验组,萃取细胞和胰岛总RNA,定量PCR分别检测INS-1细胞和胰岛组织Abcb1b、Pdx1、Ins1、Ins2、Mafa、Mafb、Ngn3、Nkx6.1、Nkx2.2、Neurod1、Pax6等基因的表达.结果 与对照组相比,P-糖蛋白过表达后,INS-1细胞Ngn3、Mafb转录水平升高(P<0.05),Mafa转录水平降低(P<0.001),其余基因表达差异无统计学意义.在野生型和转基因大鼠胰岛组织中,各基因转录水平差异均无统计学意义(P>0.05).结论 P-糖蛋白过表达可能使INS-1细胞去分化,而对胰岛β细胞的分化无明显影响.

目的 探究SD大鼠慢性睡眠紊乱后与胰岛素抵抗发生的相关性及其潜在机制.方法 选取SPF级SD雄性大鼠30只,随机分为慢性睡眠紊乱组和对照组,每组各15只.从两组中各随机选取5只大鼠处死,进行胰岛时钟基因表达的基线数据采集,其余大鼠进行后续实验.慢性睡眠紊乱组通过经典水平台法诱导慢性睡眠紊乱模型,对照组置于不含水的平台玻璃笼中,实验干预4周后,观察两组大鼠体重变化,测量空腹血糖、空腹胰岛素以及胰岛素抵抗指数(HOMA-IR)水平,同时应用实时荧光定量聚合酶链式反应(qRT-PCR)法检测胰岛昼夜节律时钟基因转录表达水平变化.采用SPSS18.0软件进行t检验.结果 实验造模前两组大鼠基线数据中各指标比较差异均无统计学意义(P＞0.05),干预4周后,与对照组相比,慢性睡眠紊乱组体重明显增加,空腹胰岛素水平、胰岛素抵抗指数明显升高,差异均有统计学意义(P＜0.05,P＜0.01);胰岛时钟基因CLOCK、BMAL1、PER1基因转录表达水平下调,而CRY1基因转录表达水平明显升高,差异均有统计学意义(P＜0.05,P＜0.01);PER2、PER3、NR1D1在转录水平表达变化差异无统计学意义(P＞0.05).结论 慢性睡眠紊乱可改变部分大鼠胰岛核心时钟基因的转录表达水平,引起大鼠体重的增加,与胰岛素抵抗的发生密切相关.

BACKGROUND Our prior study showed that patients with sleep disorders had poor blood pressure (BP), glycemic control, and more severe complications. Therefore, sleep is very important for diabetic control. Our work was to investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight and potential mechanism by a randomized parallel interventional study. METHODS T2D patients were randomly recruited to an intervention or control group. Patients received structured special diabetes sleep education program with 3-month follow-up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant. Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS 13.0 was used for statistical analysis. RESULTS One hundred patients were approached, and 45 were enrolled into our trial. Eventually, 31 patients completed the study. Patients in the intervention group greatly improved their sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48 ± 0.88 vs. -0.51 ± 0.71, P < 0.001), as well as significant reduction of HbA1c (-1.5 ± 0.55 vs. -1.11 ± 0.47, P < 0.05). Fasting plasma glucose was also lowered significantly. Homeostasis model assessment of insulin resistance was reduced significantly (-1.29 ± 0.97 vs. 1.04 ± 0.91, P < 0.01). Serum concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients -0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with HbA1c improvement. The change of ghrelin was negatively associated with the improvement of HbA1c. CONCLUSION Diabetes sleep education could improve sleep quality, better blood glucose and BP, and decrease insulin resistance through healthier sleep hygiene. Lower serum concentration of ghrelin might be partly involved in the reduction of HbA1c.

OBJECTIVE To analyze the distribution and drug resistance of pathogenic bacteria and related factors in patients with type 2 diabetes mellitus (T2DM) complicated with urinary tract infections, so as to provide references for infection prevention and control.METHODS A total of 502 patients with T2DM from Jun.2014 to Oct.2016 were selected as the research subjects.The incidences and related factors of urinary tract infections in the patients were observed and analyzed.The distribution and drug resistance of the pathogenic bacteria in the infected patients were detected.RESULTS Totally 126 cases of patients were with urinary tract infections, and the infection rate was 25.1%.A total of 131 strains of bacteria were isolated.The main pathogens were 104 strains of gram-negative bacteria, accounting for 79.4%.The drug resistance rates of gram-negative bacteria to ampicillin and ciprofloxacin were high, and no straits resistant to imipenem were detected.Logistic regression analysis results showed that the age, hospitalization time, combined antimicrobial drugs application, fasting plasma glucose level, glycosylated hemoglobin level, and duration of diabetes were independent risk factors of T2DM complicated with urinary tract infection (P<0.05).CONCLUSION The distribution and drug resistance of pathogenic bacteria and the related factors in patients with T2DM complicated with urinary tract infection have certain characteristics.The clinical medical staff should apply close monitoring and effective interventions to improve the efficiency of infection prevention and treatment, so as to improve the prognosis of the patients.

The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in β-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.

Objective To observe the effect of exogenous insulin on the expression of P-glycoprotein (P-gp)and the secretion of insulin in pancreatic beta cells (INS-1 832/13).Methods Insulinoma cells (INS-1 832/13) were cultured with 0.5 μmol/L exogenous insulin for 30 days.MTT assay was used to measure cell viability.Quantitative RT-PCR and western blot were used to detect the expression of P-gp mRNA and protein respectively,and glucose stimulated insulin secretion (GSIS) were measured by radioimmunoassay.Results Compared with control group,0.5 μmol/L exogenous insulin promoted the viability of INS-1 832/13 cells [(102.00±12.99) vs (356.00±35.51),P<0.05] and accelerated P-gp expression [(107.50±17.08) vs (307.50±44.25)] both at mRNA and protein levels [(105.00±12.91) vs (192.50±35.94),P<0.05].Glucose stimulated insulin secretion was positively correlated with P-gp expression level,but had no significant effect on basal insulin secretion.Conclusion Exogenous insulin can promote the secretion function of INS-1 832/13 cells,and the mechanism may be related to the expression of P-gp.

Objective To explore the role of interleukin-1 (IL-1) in human islet amyloid polypeptide (iAPP) related pancreatic islet cell toxicity. Methods Pancreatic islets were isolated from adult Wistar rats and the cell vitality was identified. The islets were divided into control islets (group A), 10μmol/L iAPP incubated islets (group B), 10 μmol/L iAPP plus 10 mg/L IL-1 receptor blocker (IL-1Ra) co-incubated islets (group C) and incubated for 24 h. Annexin-V/propidium iodide (PI) double-staining was used to detect islet cell apoptosis. The expressions of inflammation-related and apoptosis-related genes Bax Bcl-2 mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Independent sample t test was used for comparison between two groups. LSD test was used to compare the differences among three groups. Results (1) The apoptosis ratio and apoptosis-related gene expression:the apoptosis ratio in group B increased significantly than those in group A [(16.8 ± 4.7) % vs (1.2 ± 0.4) %]; while the apoptosis ratio in group C[(4.4 ± 2.1) %] was significantly lower than those in group B (t=5.72, 4.17, respectively, both P<0.05). Consistently, the expression of Bax mRNA increased (2.28 ± 0.46) times and Bcl-2 mRNA decreased (0.42±0.18) times in group B than those in group A (t=4.27, 3.10, respectively, both P<0.05). The expression of Bax mRNA decreased (0.48 ± 0.17) times and the expression of Bcl-2 mRNA increased (1.93±0.25) times in group C than those in group B, respectively (t=3.41, 3.23,respectively, both P<0.05). (2) The expressions of the inflammatory factors:the expressions of IL-1βand tumor necrosis factor increased by (4.25±1.64) times and (3.19±1.04) times in group B than those in group A, respectively (t=3.39, 3.49, respectively, both P<0.05);While they decreased by (0.32±0.11) times and (0.28±0.11) times in group C than those in group B, respectively (t=2.94, 3.65, respectively, both P<0.05). Conclusions The apoptosis of iAPP is associated with inflammation and IL-1 may play an important role in the pathogenesis of iAPP related pancreatic islet cell toxicity.

OBJECTIVE To study the drug‐resistant phenotypes and genotypes of Pseudomonas aeruginosa (PA ) strains from diabetic foot infective patients and investigate beta‐lactam antibiotic resistance genes of these PAE iso‐lates so as to make a preliminary discussion of the trend of β‐lactam resistance genes .METHODS The samples of foot deep tissue of 209 patients with diabetic foot admitted from Nov .2009 to Jan .2011 were collected .DNA de‐tection was conducted to the 41 strains of PAE isolated from those samples .Drug resistant genes were detected by PCR .And drug resistant genotypes and phenotypes were analyzed according to drug sensitivity test reports . RESULTS In drug resistant PAE strains ,14 carried OXA‐10(34 .15% )and 2 carried SHV (4 .88% ) and 1 strain carried both DHA ,OXA‐10 and CARB (2 .44% ) .Among them ,13 strains were found to be lack of oprD2 (31 .71% ) and 34 strains were with drug resistance phenotypes (82 .92% ) .Totally 20 strains were resistant to o‐ver 3 kinds of cephalosporin (58 .82% ) . There were 7 strains sensitive to all antibiotics (17 .07% ) . CONCLUSION The most predominant genes response to beta‐lactam antibiotic resistance of the PAE isolates in Tianjin are OXA‐10 and its derivatives .

Sodium-glucose co-transporters 2 (SGLT2) inhibitors is a new drug used for the treatment of type 2 diabetes,which can directly decrease blood glucose concentration by blocking reabsorption of filtered glucose in the renal tubule.Nowadays,many clinical studies of SGLT2 inhibitors with the type 2 diabetes were developed in the US,Europe and Japan.These researches showed that SGLT2 inhibitors performed better in reducing HbA1c,fasting plasma glucose (FPG),body weight and had less side effects.