目的 分析M蛋白阳性患者疾病谱的构成,比较不同疾病之间血清免疫学特征的差异.方法 选取M蛋白阳性住院患者211例,分析病种分布并比较不同疾病免疫球蛋白(Ig)及轻链检测结果的差异.结果 在M蛋白阳性患者中,发病率居前3位的依次为多发性骨髓瘤(MM)(53.0％)、意义未明丙种球蛋白血症(MGUS)(25.6％)、POEMS综合征(7.6％).MM患者M蛋白对应的Ig和轻链检测结果均高于MGUS和POEMS综合征患者(P<0.05),非对应的Ig和轻链检测结果均低于MGUS和POEMS综合征患者(P<0.05),而MGUS患者与POEMS综合征患者之间不同类型的Ig和轻链检测结果差异均无统计学意义(P>0.05).结论 M蛋白阳性患者中不同类型的M蛋白对应的疾病谱不同,且不同疾病之间Ig和轻链水平存在差异.

[Objective] To investigate glucose transporter 4(GLUT4) protein content in skeletal muscle cells of early-onset T2DM and to evaluate its potential molecular mechanism in the pathogenesis of early-onset T2DM. [Methods] Totally 28 patients given opportunity selected operation were enrolled and all agreed the consent. They were divided into four groups: Young non-diabetic control group (YN, n =6), Old non-diabetic control group (ON, n=6), Early-onset T2DM group(EOD, n =8), Late-onset T2DM group (LOD, n =8). The fasting blood was taken on the day before operation to determine the fasting blood glucose(FPG), HbA1c and fasting insulin(FINS). About 500 mg skeletal muscle was removed during the operation for GLUT4 protein analysis. The technique of Western blot was used to detect the concent of GLUT4 protein in skeletal muscle cells. [Results] The value of FPG and HbA1c in diabetic group were higher than those in non-diabetic group. Compared with LOD group, the mean value of FPG and HbA1c were significantly higher in EOD group. The level of GLUT4 protein content in diabetic group was lower than that in non-diabetic group. Compared with LOD group, the level of GLUT4 protein was higher in EOD group(P0.05). In diabetic group the content of GLUT4 protein was negatively correlated with WHR, HOMAIR and waist. [Conclusion] The content of GLUT4 protein of skeletal muscle may play a role in insulin resistance in type 2 diabetes mellitus. Compared with LOD group, the relative high level of GLUT4 protein in skeletal muscles cells may associated with lower insulin resistance in EOD group.

Objective:Surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) is a no- vel method for biomarker discovery that can provide a rapid protein expression profile.The current study was undertaken to in- vestigate urinary protein profile of isolated impaired fasting glucose patients with normal albuminuria.Methods:Urine of 20 NGT and 22 IFG without elevated ACR were analyzed using surface enhanced laser desorption/ionization time of-flight mass spectrometry (SELDI-TOF-MS) and potential differences in protein or polypeptide profile were identified by Biomarker Wizard Software.Results:Protein profile of urine showed the best peak spectrum on IMAC-Cu2+arrays by sensitivity of 9 and laser intensity of 230.The intensities of protein/polypeptide peaks appeared upregulated in IFG group at M/Z2200、2353、2443、2579、2755、2797、2910、3003、3097、3606,3645、4029 and 5511,but downregulated at M/Z5083.Conclusion:SELDI is powerful and high throughput in comparative proteomic analysis.Small molecular proteins and/or polypeptides excretion may abnormal in IFG with normal urinary albumin.

Objective:To observe insulin resistance status in the impaired fasting glucose subjects by new cut point. Methods: 62 healthy volunteers were divided to group NGT(n = 16) ,IFG(n = 26) and CGT(n = 15) according to the results of OGTT. Fasting plasma glucose, fasting insulin, fasting C peptide, triglyceride, cholesterol and 2 h blood glucose,insulin and C peptide in OGTT were measured. Insulin sensitivity andβcell function were evaluated by HOMA index. Results: HOMA-IR was higher in group IFG and group CGT than those in group NGT. No significant difference was observed among three groups. Conclusion: Insulin resistance existed in the impaired fasting glucose subjects, no matter whether combined with impaired glucose tolerance.

Purpose To investigate the change of insulin resistance(IR),function of β-cell and its correlative factors. Methods Subjects of diabetic patients grouped by newly diagnosed and by five years duration added till to greater than 15 years(DM,n=841),isolated impaired glucose tolerance(IGT,n=29),normal glucose tolerance(NGT,n=133) were studied.Body mass index(BMI),waist hip ratio(WHR),blood pressure(BP),blood lipid,fasting plasma glucose(FPG),fasting insulin(FINS) were compared among the groups.Homeostasis model assessment(HOMA) was applied to assess the status of β-cell function(HOMA-β) and insulin resistance(HOMA-IR). Results During the progression to diabetes,FINS increased along with the gradually elevated glucose level.In newly diagnosed diabetes,it reached to its maximal peek,and then slowly declined.There was no significant difference between NGT and IGT in HOMA-β,but in the groups of DM,HOMA-β were notably decreased along with the course of disease.When compared to NGT,HOMA-IR was already much higher in IGT,and still remained at high level in DM.Pearson correlation analysis demonstrated that course of disease,FPG were negatively correlated with HOMA-β(P0.001);course of disease,BMI,WHR,diastolic blood pressure(DBP),FPG,FINS and triglyceride(TG) were positively correlated with HOMA-IR(P0.001). Conclusions Insulin resistance is already existed in IGT status.Islet β cell function decreased gradually from NGT to DM,insulin resistance throughout the transition.They are correlated with FPG,BP,blood lipid,and obsess.

胎儿生长发育机制目前尚不完全清楚,营养物质(葡萄糖)-胰岛素-胰岛素样生长因子代谢轴可能是调节胎儿和生后早期生长的中心环节[1].

Objective To investigate the effect of dietary fatty acids composition on insulin resistance in OLETF rats. Methods Forty 14-week-old male Otsuka Long-Evans Tokushima Fatty(OLETF) rats were ran-domizedly divided into 4 groups(n = 10, each). They were fed with standard diet(A) , high fat diet(C) , high n-6 polyunsaturated fatty acid(PUFA) diet(D) and high n-3 PUFA diet(E), respectively for 10 weeks. Ten male LE-TO rats served as control were fed with standard diet. Oral glucose tolerance tests, C peptide and immunoreactive insulin(IRI) were measured. Hyperinsulinemia clamp was used to evaluate the insulin resistance of the rats. Results At the age of 24-weeks, all OLETF rats except group E had higher levels of fasting plasma glucose, 120' postloading plasma glucose and IRI than those of the control group(P < 0.05). However, the levels of fasting and 120' postloading C peptide were similar in all groups. In addition, LETO and group E rats had higher level of glucose infusion rate than group C and D rats(P < 0.05). Conclusion The OLETF rats had higher levels of plasma glucose and lower insulin sensitivity than the LETO rats, suggesting that diet with high n-3 PUFA may improve glucose metabolism and insulin resistance in OLETF rats.

The effect of diet with various fatty acid composition on insulin resistance in male OLETF ratswas observed. The results showed that it was beneficial to insulin sensitivity in rats fed with ω 3 polyunsaturated fatty acid rich food.

目的研究不同脂肪酸组分的饮食对OLETF大鼠尿铜蓝蛋白的影响.方法将40只OLETF大鼠随机分为4组,按不同组分脂肪酸配成的饲料喂养,LETO大鼠10只,作为对照,从第14周开始直至24周每隔两周留尿,测定尿铜蓝蛋白(U.cP)和肌酐(Cr),计算cP/Cr指数;每二周一次.分析不同组分饲料喂养对OLETF大鼠尿铜蓝蛋白的影响.结果所有大鼠自14周至24周,尿铜蓝蛋白/肌酐逐渐上升,对各周不同组大鼠尿铜蓝蛋白/肌酐进行比较后发现,LETO大鼠在各周次均明显低于OLETF大鼠,OLETF大鼠中,A组和E组无显著性差异,C组明显高于A组和E组,而D组则较A组、C组和E组高.结论进食富含11.3PUFA饲料,有益于降低OLETF大鼠尿铜蓝蛋白.

Objective To observe the effects of glucagon-like peptide-1 agonist exendin-4 on glucose and insulin level and the expression of transcription factor pdx-1 mRNA in diabetic animal model OLETF rat with genetic insulin resistance. Methods OLETF rats randomly divided into 4 groups: vehicle(control),exendin-4 doses of 5 μg/kg(EX4 A),20 μg/kg(EX4 B)、 100 μg/kg(EX4 C).The exendin-4 was injected daily.Oral glucose tolerance test and insulin release test were performed after 7 days treatment.The pdx-1 mRNA expression was detected by RT-PCR.Results Glucose tolerance was improved in EX4 groups,fasting and postprandial glucose and peak glucose levels were significantly lower and insulin secret was statistically increased than in control group,P0.05.The HOMA-B in EX4 groups(98.18±29.14,73.74±22.19,135.86±58.62 respectively)were also improved, much higher than that of 36.88±15.14 in control group,P0.05.While HOMA-IR were not significantly different in statistics among EX4 A,EX4 B and control groups.The expressions of pdx-1 mRNA in three EX4 groups were 0.40±0.15,0.56±0.15 and 0.65±0.1,notably elevated than 0.24±0.13 in control group,P0.05.Conclusions The exendin-4 treatment enhances insulin secret,decreases glucose level,improves glucose tolerance and B-cell function,and up-regulates the pdx-1 mRNA expression in OLETF rat.

AIM: To investigate the effects of exendin-4 on glucose level and glucose tolerance in non-diabetic mice. METHODS: Non-diabetic mice were divided into exendin-4 and normal saline (NS) groups. After a bolus intraperitoneal administration of 0.1 μg·g -1 exendin-4, glucose levels were tested at 1 h after administration, followed by daily 10 d of injection and after the injection of 2 wk. Intraperitoneal glucose tolerance test (IPGTT) was performed on d 20 after the cessation. In addition, three different doses of exendin-4 (0.1, 0.2, 0.4 μg·g -1) were injected daily for 3 d and glucose levels were also tested daily during the injection. RESULTS: The glucose level of mice treated with 0.1 μg·g -1 exendin-4 1 h after the injection was significantly lower as comparing to NS treated mice, ((6.2±s 1.3) mmol·L -1 vs (10.6±1.1) mmol·L -1,P0.01). The average glucose levels were not affected either during the injection or after the cessation. The results of IPGTT also showed no statistical difference between the two groups. Different doses of exendin-4 did not show notable difference in comparing to the NS group. CONCLUSION: The instant effect of exendin-4 on non-diabetic mice is to decrease glucose level, but daily injection shows no significant influence on glucose level and glucose tolerance.

Exendin-4 treat ment decreased the amount of foodintake and body weight ,i mprovedβ-cell function and glucose tolerance ,and restored early-phase insulin secretionin OLETFrats of spon-taneous type 2 diabetes model ,compared with placebo treat ment of diabetic OLETF and with non-dia-betic inbreed of LETOrats .

Objective To observe the effects of exendin 4 on blood glucose level, number of islets and expression of pdx-1 in streptozotocin (STZ) treated mice. Methods Thirty C57BL/6 mice were divided into 3 groups:controlgroup(vehicle),STZgroup (STZ 50 mg/kg+vehicle) and STZ+exendin 4 group (STZ 50 mg/kg+exendin 4 0.1 μg/g weight). Mice were intraperitoneally injected with exendin 4 or vehicle daily for 10 days. From day 3 to day 7, some of the mice were injected with STZ. Blood glucose level was tested during 10 days of injection and two weeks after injection. On day 30, intraperitoneal glucose tolerance test (IPGTT) was performed and the number of islets was counted and the gene expression of pdx 1 was detected by RT PCR. Results The average blood glucose level in STZ+exendin 4 group [(6.12±0.37)mmol/L] showed no significant difference from that of control group [(6.21±0.41)mmol/L, P>0.05],butwaslowerthanthatof STZ group [(9.59±1.08)mmol/L, P<0.05]. During the two weeks after the cessation of exendin 4 injection, the blood glucose level in STZ+exendin 4 group was still lower than that of STZ group [(13.02±1.96 vs 18.55±3.14)mmol/L, P<0.05]. As compared with STZ group, STZ+exendin 4 group showed improvement in glucose tolerance, increment of islet number (by 100%), and up regulation of pdx 1 expression. Conclusion Exendin 4 exhibits a brief as well as long term benefit in STZ treated mice. It improves glucose tolerance, increases number of islets and up regulates expression of pdx-1 mRNA.

Objective To investigate the effectiveness of exendin-4 on glucose level of streptozotocin(STZ)-induced diabetic mice. Methods Male eight-week-old C57BL/6 mice were divided into six groups: aqua-injected group, exendin-4 0.1 μg/g weight group, STZ group, STZ+exendin-4 (0.1, 0.2, 0.4 μg/g weight) groups. The blood glucose levels were determined on the first 10 days during the treatment and on day 12, 15, 18, 24 after the treatment. All mice were subjected to an intraperitoneal glucose tolerance test (IPGTT) on day 30. Results There was no statistical difference between the groups of aqua-injected group and exendin-4 groups 0.1 μg/g weight group during and after the treatment. As compared with STZ treated group only, STZ+varying doses of exendin-4 groups showed a lower blood glucose level throughout the study (P 0.05); the 0.1 μg/g weight dose gave the best result, there was no significant difference as compared with the aqua-injected group in normal mice (P 0.05), and there was no notable difference among the three groups after the treatment. The results of IPGTT on 30th day showed no distinct difference either.Conclusion Exendin-4 would not lead to hypoglycemia in normal mice but can improve the hyperglycemia in STZ-induced diabetic mice, it also has a prolonged effect on blood glucose level independent of dose.

目的:探讨孕晚期脂肪细胞膜脂肪酸组成与胰岛素抵抗的关系.方法:正常妊娠40例,妊娠期糖尿病(GDM)孕妇41例,以胰岛素敏感指数(ISI)评价胰岛素抵抗程度;在剖宫产时随机抽取正常妊娠和GDM孕妇各10例,取皮下脂肪各10g,用气相色谱法测定脂肪细胞膜脂肪酸.结果:GDM孕妇ISI为4.25±0.51,明显高于正常孕妇的3.52±0.56,(P＜0.001).GDM脂肪细胞膜饱和脂肪酸(SFA)百分含量为30.42±1.16,高于正常妊娠的26.92±3.63(P＜0.05);多不饱和脂肪酸(PUFA)百分含量为25.94±2.82,明显低于正常妊娠的30.27±3.21(P＜0.01),单不饱和脂肪酸(MUFA)百分含量为43.64±3.31,正常妊娠为42.81±1.80,差异无显著性(P＞0.05).对ISI与脂肪细胞膜脂肪酸饱和程度偏相关分析,ISI与脂肪细胞膜SFA含量呈正相关(r=0.5541,P＜0.05);与脂肪细胞膜PUFA含量呈负相关(r=-0.5293,P＜0.05);与脂肪细胞膜MUFA无相关.结论:GDM的胰岛素抵抗可能与脂肪细胞膜多不饱和脂肪酸减少有关.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的　观察富含n - 6和n - 3多不饱和脂肪酸 （PUFA）饲料对自发性 2型糖尿病模型OtsukaLong -E vansTokushimaFatty（OLETF）大鼠糖代谢及血清磷脂 （S -PL）中脂肪酸 （FA）组成的影响。 方法　将 2 0只 14周龄雄性OLETF大鼠随机分为 2组。两组大鼠饲料总能量相同 ,其中饱和脂肪酸 （SFA）、单不饱和脂肪酸 （MUFA）和PU FA的百分含量亦相同 ,但分别富含n - 6PUFA〔4 1 6mol/ （10 0mol·脂肪 ）〕和n - 3PUFA〔2 0 4mol/ （10 0mol·脂肪 ）〕 ,饮食干预 10周。第 2 4周时实施口服糖耐量试验 （OGTT）、胰岛素水平测定和S -PL中FA组成测定。结果　干预期间 ,两组大鼠总进食量及体重增长无显著性差异 ;干预后OGTT及胰岛素水平测定表明 ,n - 3组相对于n - 6组具有较好的胰岛素敏感性。n - 3组大鼠S -PL中 18∶1（n - 9）、MUFA总量、18∶2 （n - 6 ）、各n - 3系PUPA百分含量较n- 6组高 ,n - 6PUFA总量、2 0∶4 （n - 6 ）百分含量较低。结论　n - 3PUFA的摄入相对于n - 6PUFA对OLETF大鼠的糖代谢有益 ,OLETF大鼠S -PL的FA组成受到饲料中FA的影响 ,但并不是其直接反应。</span>

研究表明,肾脏存在丰富的瘦素受体的转录表达[1],近来报道给予大鼠瘦素后刺激肾小球内皮细胞增殖并刺激内皮细胞合成转化生长因子(TGF)β,引起肾小球系膜基质的扩张和尿蛋白排泄率增加[2],提示瘦素在肾脏的致病作用.目前对于糖尿病动物模型肾脏瘦素受体的分布、类型了解甚少,本研究旨在观察瘦素受体在链脲佐菌素(STZ) 糖尿病大鼠肾脏中的转录表达及在肾脏的免疫组化定位.

Purpose Chronic diabetic complications like diabetic nephropathy(DN) have been the major death cause of diabetes mellitus,early detection and intervention of DN in microalbuminuria stage or early may reverse the kidney lesion,microalbumin measurement has been the wide accepted standard for DN early screening for several decades,but studies have shown it not fully correlated with kidney pathological changes,so,exploring new measurement for the early detection of DN has been one of the focus of DN researches.The aim of present study is to exploring the value of urinary ceruloplasmin screening in the early detection of diabetic nephropathy in children and adolescents with type 1 diabetes mellitus(T1DM) in contrast to the urinary microalbumin examination. Methods Forty cases of T1DM children and adolescents,twenty-one cases of nephrotic syndrome children and sixty cases normal children were recruited.Twenty four hours urine was collected and the urinary ceruloplasmin and albumin were detected by ELISA and radioimmnunoassay respectively. Results The urinary ceruloplasmin creatinine ratio(UCp/Cr) (median 1.08 ng/min) and urinary albumin excretion rate(UAER) (median 6.84 μg/min) in T1DM and nephrotic syndrome groups(UCp/Cr median 1.8 ng/mmol,UAER median 6.29 μg/min) were significantly increased comparing with normal control(UAER median 1.94 μg/min;UCp/Cr median 0.08 ng/mmol;P0.05).47.5% of T1DM patients were found with abnormal excretion of urinary ceruloplasmin and 10% with microalbuminuria.UCp/Cr was significantly increased in UAER≥20 μg/min group(UCp/Cr median 2.65 ng/mmol) than UAER20 μg/min group(UCp/Cr median 0.34 ng/mmol,P=0.02).UAER in diabetic patients with duration less than 2 year(UAER median 4.9 μg/min) was 1.44 times than that of duration more than 10 years(UAER median 7.08 μg/min),meanwhile,UCp/Cr in DM patients with duration less than 2 year(UCp/Cr 0.28 ng/mmol) was 2.54 times than that of duration more than 10 years(UCp/Cr 0.71 ng/mmol).The change of UCp/Cr in T1DM children and adolescents was significantly correlated with HbA 1c( r=0.45,P=0.01) and UAER( r=0.47,P=0.002). Conclusions Like early DN kidney lesion,lose of negative charge selectivity was the typical change of nephrotic syndrome(NS),UCp in NS control was significantly increased than normal control and positively correlated with UAE,so,the leakage of urinary ceruloplasmin in TIDM adolescents may due to the same change.Because the more significant increase of UCp/Cr in longer DM duration patients than UAE and more abnormal ratio of UCp/Cr than UAE in type 1 diabetes patients,urinary ceruloplasmin screening may be a potential more sensitive and noninvasive mark of early diabetes kidney lesions.

Objective To investigate the insulin resistance status in male OLETF rats and its relationship to some associated factors. Methods 10 male OLETF rats and 10 male LETO rats (as control) of 14 weeks old were selected. The amount of daily food intake, body weight, and visceral fat content were recorded. Urine was collected for measuring Alb/Cr and Cp/Cr indexes, and fasting blood sample for lipid profile. Skeletal muscle was fetched after sacrificed for the analysis of fatty acid composition. Hyperinsulinemia clamp was used to evaluate the insulin resistant status of the rats.Results Compared with LOET rats, the characteristics of OLETF rats were: ①more daily food intake; ② higher body weight; ③ higher serum TG and CH levels; ④ higher Cp/Cr index; ⑤ higher blood glucose le vels in OGTT except fasting ones; ⑥ lower GIR; ⑦ higher n 6 PUFA and lower n 3 PUFA, with similar total PUFA composition.Conclusion Despite of NGT, insulin resistance had already existed in 14 weeks old male OLETF rats simultaneously manifesting higher body weight, high visceral fat deposition and elevated TG. CH levels associaled with significant change of fatty acid composition in the skeletal musle

Purpose To establish a gas chromatography (GC) method for the determination of 23 fatty acids in serum. Methods The extracted lipids were methylesterized by 14% BF3 at 80℃ for 40 min, then separated and measured by GC17A Shimadzu system equipped with a DB - 23 (30 m ×0. 25 mm ×0.25μm) glass capillary column and a flame ionization detector, with nitrogen as the carrier gas. A temperature program accompanied by pressure program was designed, that is, column temperature raised from 140 ℃ to 234 ℃(rate:3℃ /min) ,meanwhile,column pressure raised from 130 kPa to 163 kPa(rate: 1 kPa/min). Results The limit of detection of 16:0,18:0 and 18 : 1n9c were 3. 6 ×10-11g,2. 4 ×10-11g,2. 4× 10-11g,respectively. In the range from 3.2 to 600 ng/μL,there was a linear relationship between the areas and concentrations (r 0.990). The method recovery was good (84.40 % - 104.12 % ), and the within-day RSD and between-day RSD were less than 10% . Conclusions This method proved to be specific, sensitive and reproducible, and applicable for the determination of fatty acid composition in serum.