钙蛋白酶10基因多态性与高血压家族史及血糖水平的关联

目的　分析高血压家系和非高血压家系后代 ,钙蛋白酶 10 (CAPN 10 )基因多态性与高血压家族史、血糖水平的关联。方法　测定大庆地区 187个高血压家系和 191个非高血压家系第二代直系亲属的空腹血糖、胰岛素、甘油三酯和纤维蛋白原 ,用聚合酶链反应 (PCR)单链构型多态法(SSCP) ,DNA测序分析CAPN 10基因多态性。结果　 (1)高血压及非高血压家系的第二代直系亲属中CAPN 10基因UCSNP 4 3G/G型频率分别为 86 6 %、75 4 % (P <0 0 5 ) ;该基因型携带者在有高血压家族史有高血压人群明显多于无高血压家族史非高血压人群 (OR为 2 84 ,P =0 0 1)。 (2 )多因素分析 ,排除年龄、性别和体重指数影响后 ,空腹血糖最高四分变量组 (5 4 2± 0 1)mmol/L比最低四分变量组(4 0 9± 0 3)mmol/L携带该基因型明显增多 (OR值为 3 32 )。结论　CAPN 10基因UCSNP 4 3可能是大庆地区原发性高血压和糖尿病的遗传因素之一 ,其中G/G型对于预测高血压患者后代是否发生 2型糖尿病有一定作用     

胰岛素受体底物1基因Gly972Arg多态性与2型糖尿病不相关

目的：探讨中国汉族人群胰岛素受体底物1（IRS－1）基因Gly972Arg多态性与2型糖尿病的关系。方法：选取102例2型糖尿病患者及102例糖耐量正常的患者配偶进行对照研究，应用聚合酶链反应－－限制性片断长度多态性的方法进行胰岛素受体底物1基因Gly972Arg多态性位点基因型检测。结果：IRS－1基因Gly972Arg突变频率在病例组和对照组均为2％，明显低于白人。结论：在中国汉族人群中，IRS－1基因Gly972Arg突变不是2型糖尿病的主要致病因素。     

β1肾上腺受体Arg389Gly多态性与β1受体阻滞剂降压疗效的相关性研究

目的探讨β1肾上腺素受体(β1-Adrenergic Receptor,ADRB1)Arg389Gly基因多态性与ADRB1阻滞剂降压疗效的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析412例原发性高血压患者ADRB1Arg389Gly基因多态性,将患者分成Arg389Arg组,Arg389Gly组和Gly389Gly组,观察比索洛尔治疗8周后血压变化的组间差异。结果比索洛尔治疗8周后,Arg389Arg组,Arg389Gly组和Gly389Gly组收缩压(SBP)分别下降了12.1%±4.5%,3.4%±4.1%和1.3%±1.0%,舒张压(DBP)分别下降了6.9%±4.4%,2.5%±4.1%和0.8%±4.0%,修改为收缩压(SBP)分别下降了(12.1±4.5)mmHg,(3.4±4.1)mmHg和(1.3±1.0)mmHg,舒张压(DBP)分别下降了(6.9±4.4)mmHg,(2.5±4.1)mmHg和(0.8±4.0)mmHg。组间比较差异均有统计学意义(均P0.01)。结论ADRB1的Gly389Arg基因多态性与比索洛尔降压疗效相关。     

海南汉族2型糖尿病患者胰岛素受体底物1基因Gly972Arg多态性的研究

目的 研究胰岛素受体底物1（IRS。1）基因Gly972Argr矢变与海南汉族2型糖尿病（T2DM）的关系。方法应用聚合酶链反应-限制性片段长度多态性技术对海南汉族60例T2DM患者和60例糖耐量正常人群进行IRS-1基因Gly972Arg突变位点基因型检测。结果T2DM组IRS-1基因Gly972Arg突变频率13．3％,对照组IRS-1基因Gly972Arg突变频率3．3％,两者比较有统计学差异（r=7．2,P〈0．01）。结论IRS—1基因Gly972Arg突变可能与海南汉族T2DM的发生有相关性。     

高血压患者胰岛素与血糖交互的关系

目的 探讨高血压患者胰岛素(INS)水平变化与血糖的关系.方法 选取单纯高血压、高血压伴代谢综合征(MS)和健康体检者(对照组)各40例,8:00-9:00空腹测量血压、并抽血检测空腹血糖(FPG)、空腹胰岛素(FINS),然后口服75 g葡萄糖2 h后抽血检测血糖和INS, 用单因素方差分析判定各组间参数差异的统计学意义,用多因素方差分析血糖、INS与高血压的交互影响情况.结果 单纯高血压[FPG(5.27±0.67)mmol/L,2 h PG(6.38±0.66)mmol/L,FINS(21.5±5.7)μIU/mL,2 h INS(73.6±28.3)μIU/mL,HOMA-IR(4.9±1.8)]与对照组比较,FPG和胰岛素抵抗指数差异有统计学意义;高血压伴MS组[FPG(5.28±0.65)mmol/L,2 h PG(8.78±0.75)mmol/L,FINS(28.0±7.3)μIU/mL,2 h INS(129.2±47.1)μIU/mL,HOMA-IR(12.5±5.1)]与对照组比较,全部观察指标差异均有非常显著意义;血糖、胰岛素与纯高血压组之间无交互现象.结论 高血压患者存在胰岛素和糖代谢紊乱;单纯高血压血糖、胰岛素水平变化与高血压伴MS者有明确的不一致性.     

β2-肾上腺素能受体多态性/单倍型与支气管哮喘表型的相关性

目的 研究β2-肾上腺素能受体基因的多态性/单倍型与支气管舒张剂的反应性及血清免疫球蛋白E的负对数(lgIgE)间的关系.方法 2006年2月至2007年2月采用DNA测序法测定了201例哮喘患者(哮喘组)和276名健康对照者(健康对照组)的β2-AR基因5个位点(-47、-20、46、79、252)的基因型并确定其单倍型.统计学处理采用SPSS 11.5软件.以拟和优度的x2检验计算各位点基因型频率是否符合Hardy-Weinberg平衡.5个位点基因型的频率比较采用卡方检验,位点间的连锁不平衡采用确切概率法,不同基因型及单倍型与定量指标间的比较采用方差分析.如果方差分析有统计学意义,则用LSD方法对各组间的值进行两两比较.结果 哮喘组中Arg16Arg16基因型患者的支气管舒张剂反应性为(13±4)L,与Arg16Gly16基因型[(7±3)L]及G1y16Gly16基因型[(7±3)L]比较差异有统计学意义(F=81.55,P＜0.01);在哮喘组6种单倍型中,单倍型Arg16Gln27/Arg16Gln27的△FEV1最高[(13.4±3.5)L],与其他种单倍型[Gly16Gln27/Gly16Gln27(6.4±0.6)L、Gly16Glu27/Gly16Glu27(7.6±3.1)L、Gly16Gln27/Gly16Glu27(6.9±3.5)L、Gly16Gln27/Arg16Gln27(7.2±3.3)L及Gly16Glu27/Arg16Gln27(7.9±2.7)L]比较差异有统计学意义(F=32.55,P＜0.01);哮喘组中Gln27Gln27基因型患者的血清lgIgE为(2.51±0.33)IU/L,与Gln27Glu27基因型患者的血清lgIgE[(2.30±0.82)IU/L]比较差异有统计学意义(F=3.89,P＜0.05);哮喘组中单倍型Gly16Glu27/Arg16Gln27的血清lglgE最低[(2.13±0.15)IU/L],与其他4种单倍型[Arg16Gln27/Arg16Gln27为(2.56±0.14)IU/L、Gly16Glu27/Gly16Glu27为(2.40±0.16)IU/L、Gly16Gln27/Gly16Glu27为(2.54±1.26)IU/L、Gly16Gln27/Arg16Gln27为(2.48±0.48)IU/L]比较差异有统计学意义(F=3.56,P＜0.01).结论 依据所研究的哮喘表型,无论是β2-AR基因的多态性,还是单倍型均可能影响疾病的表现.     

原发性高血压人群胰岛素抵抗与β_3-肾上腺素能受体基因多态性的关联

目的　对中国汉族原发性高血压人群中胰岛素抵抗与 β3 肾上腺素能受体 (β3 AR)基因多态性的关系进行探讨。方法　 179名原发性高血压患者 ,以胰岛素敏感指数〔IAI =-ln(空腹血糖×空腹血胰岛素 )〕5 0百分位点将此人群划分为胰岛素相对抵抗组 (IAI≤ - 4.88)及胰岛素相对敏感组 (IAI>- 4.88) ,并以 42名正常人作为对照。测定血压、空腹血糖、空腹血胰岛素、血脂、尿酸等指标 ,并提取DNA进行 β3 AR基因 6 4位T/A多态性的分析。结果　β3 AR基因 6 4位Trp→Arg突变携带者的频率在抵抗组较敏感组高 (2 8.0 %vs 15 .7% ,P <0 .0 5 )。Spearman相关分析发现 β3 AR基因型与IAI呈负相关 ,与血清甘油三酯、总胆固醇、尿酸水平正相关 (P <0 .0 5 )。运用Logistic回归分析 ,总人群中β3 AR基因突变型与胰岛素抵抗显著相关 ,相对危险度为 2 .36 (95 %可信限 1.10～ 5 .0 6 ,P <0 .0 5 )。结论　原发性高血压人群中 β3 AR基因 6 4Arg突变携带者易发生胰岛素抵抗 ,此突变与高甘油三酯、高胆固醇、高尿酸血症相关。β3 AR基因 6 4位Trp→Arg突变可能是部分高血压患者胰岛素抵抗的遗传基础     

关于空腹血糖、空腹胰岛素乘积的倒数在流行病学研究中应用的补充说明

高胰岛素正糖钳夹技术可以测定活体的胰岛素敏感性,但它并不适用于大规模流行病学研究。流行病学研究需要简单的胰岛素抵抗测定法。本文补充报告在空腹血糖(FPG)(75～306mg/dl或4.2～17.1mmol/L)及空腹胰岛素(FIns)(9.7～120mU/L)范围很宽的Pima印第安人群中,正糖钳夹技术测定的胰岛素介导的葡萄糖代谢率(M)与涉及FPG、FIns的多种复合的胰岛素敏感指数的相关性:胰岛素作用指数(IAI)=1/(FPG×FIns)在非糖尿病人群及2型糖尿病人群都与M显著正相关(r>0.7,P=0.0001),而且这两者的相关性强于M与其他指数如FIns或FPG/FIns比值的相关性,也不弱于M与糖负荷后3～5个时间点的血糖、胰岛素曲线下面积乘积的相关性。IAI的五分变量分布情况表明有90.4%的IAI落在所预测的M值五分变量区域或与之相邻的一个五分变量区域之内。1/FPG×FIns虽相对简单但确实与机体的胰岛素敏感性密切相关,它可以做为胰岛素敏感指数在流行病学研究中应用。     

β2肾上腺素能受体基因多态性与岳西地区高血压患者血压的关系

目的探讨岳西地区人群β2肾上腺素能受体（ADRB2）基因Arg16Gly多态性与血压相关性。方法用RFLP方法对安徽省岳西地区487例高血压病患者及672例家属的B：。肾上腺素能受体基因的Arg16／Gly多态性位点进行了检测,应用了以家系为基础的分析方法,分析了岳西地区成年高血压人群ADRB2多态位点与高血压的相关性。结果在岳西人群中,带有ADRB2 Arg16等位基因的高血压病患者的收缩压（P=0．003）和舒张压（P=0．003）水平都较低,遗传对血压的影响更适合于共显性模型。结论ADRB2基因Gly16等位基因与高血压可能存在相关关系。     

胰岛素受体底物1基因Gly972Arg多态性与海南黎族2型糖尿病的关系

目的 研究胰岛素受体底物1(IRS-1)基因Gly972Arg突变与海南黎族2型糖尿病(T2DM)的关系.方法应用聚合酶链反应-限制性片段长度多态性技术,对78例海南黎族T2DM患者(T2DM组)和78例糖耐量正常人群(对照组)进行IRS-1基因Gly972Arg突变位点基因型检测.结果 对照组IRS-1基因Gly972Arg突变频率5%,T2DM组未发现该基因突变.结论 IRS-1基因Cly972Arg突变可能不是海南黎族T2DM的重要遗传因素.     

New insights into the signaling system and function of insulin in fish

Fish have provided essential information about the structure, biosynthesis, evolution, and function of insulin (INS) as well as about the structure, evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it is not clear if they arose from a common gene duplication event or from multiple separate gene duplications. INS is produced by the endocrine pancreas of fish as well as by several other tissues, including brain, pituitary, gastrointestinal tract, and adipose tissue. INS regulates various aspects of feeding, growth, development, and intermediary metabolism in fish. The actions of INS are mediated through the insulin receptor (IR), a member of the receptor tyrosine kinase family. IRs are widely distributed in peripheral tissues of fish, and multiple IR subtypes that derive from distinct mRNAs have been described. The IRs of fish link to several cellular effector systems, including the ERK and IRS-PI3k-Akt pathways. The diverse effects of INS can be modulated by altering the production and release of INS as well as by adjusting the production/surface expression of IR. The diverse actions of INS in fish as well as the diverse nature of the neural, hormonal, and environmental factors known to affect the INS signaling system reflects the various life history patterns that have evolved to enable fish to occupy a wide range of aquatic habitats.     

胰岛素治疗使糖尿病大鼠的胰岛素抵抗逆转

链脲佐菌素引起的糖尿病大鼠用胰岛素治疗6天后,治疗组(n=4)与未治疗组(n=20)比较:(1)体重和血清胰岛素浓度显著增加,而摄食量,饮水量和血糖均显著降低;(2)脂肪细胞膜胰岛素结合率显著降低,其胰岛素受体数目减少但受体亲和力没有改变;(3)基础(不加胰岛素时)和胰岛素刺激的脂肪细胞葡萄糖氧化均显著增加。提示胰岛素治疗虽使靶细胞上胰岛素受体数目减少,但可显著提高靶细胞对胰岛素的反应性,即可使受体后胰岛素抵抗减轻。     

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy

Aims/Introduction

To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.

Materials and Methods

In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.

Results

In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.

Conclusions

The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.     

Serum insulin,insulin antibodies and insulin requirement in the first period of insulin treatment in non-insulin resistant diabetics

Summary Twelve insulin-sensitive diabetics were studied for 200 days after the initiation of mixed beef-pork NPH insulin. Normalization of the fasting blood glucose was not accompanied by any elevation in the pre-treatment fasting immunoreactive insulin level. Insulin antibodies appeared in 2 patients on the second week of insulin treatment, in 6 others within 87 days. In 4 patients no antibodies were found 200 days after the start of insulin. The appearance of antibodies was accompanied in two patients by a decrease in insulin requirement, in others there was no change. When antibodies were present, the total maximum insulin binding capacity was 4 to 12 U/1, but the total insulin constituted only 3 to 36% of the binding capacity. Insulin wastage caused by the destruction of the immune complexes was calculated to be 0.35 to 5.6 U/die only, and this explains the negligible effect of insulin antibodies on insulin requirement in non-resistant patients. Presented at the 10th Annual Meeting of the European Association for the Study of Diabetes in Jerusalem, September 11–13, 1974.     

Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series

Objectives

Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption.

Methods

Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients.

Results

When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030).

Conclusions

Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.     

Semantics of insulin

The lack of a stringent terminology and a well-defined vocabulary for insulin and related subjects has been a deterrent to solving many of the problems encountered when using insulin in pumps. The same word is sometimes used to describe a number of different phenomena or the same phenomenon is referred to by different words. Thus the word 'insulin', meaning the substance, the protein hormone, is commonly used as a synonym for an 'insulin formulation' for the treatment of diabetes. The 'insulin dimer' can be the covalent or the non-covalent dimer, two very different substances. 'Isoelectric precipitation' is often mistaken for 'fibrillation' and both are referred to as 'aggregation' or 'polymerization'. The word 'crystal' is being used as a synonym for 'particle', and determination of 'the content of insulin' by HPLC is sometimes called a 'bioassay'. The nature and consequences of these pitfalls are discussed, and advice is given on how to avoid them.     

胰岛素的糖基化作用及其与胰岛素抵抗的关系

人胰岛素在体外与不同浓度葡萄糖溶液孵育，利用氯化硝基四唑氮蓝还原反应证实胰岛素能被糖基化；利用抗胰岛素抗体分离３３例Ⅱ型糖尿病患者血清胰岛素，比色测定糖基化胰岛素水平。结果表明：糖尿病患者糖基化胰岛素水平显著升高，且与血糖呈显著正相关，与空腹血胰岛素／血糖比值和糖负荷后曲线下胰岛素／血糖面积比值呈显著负相关。说明糖基化胰岛素水平取决于血糖控制状况。且可能参与胰岛素抵抗的形成。     

链脲佐菌素糖尿病大鼠的胰岛素受体结合、胰岛素介体释放和葡萄糖氧化

作者测定了链脲佐菌素引起的糖尿病大鼠脂肪细胞膜对胰岛素特异结合率、肝细胞膜胰岛素介体释放和脂肪细胞葡萄糖氧化。结果表明:(1)糖尿病大鼠脂肪细胞膜对胰岛素特异结合率较正常大鼠显著增加,其胰岛素受体亲和力没有改变,但受体数目增加;(2)大鼠肝细胞膜加胰岛素诱导时,糖尿病鼠肝膜释放的抑制腺苷酸环化酶活力的胰岛素介体量较正常大鼠显著减少;(3)在糖尿病大鼠,基础的和胰岛素刺激的脂肪细胞葡萄糖氧化较正常大鼠显著降低。提示胰岛素介体释放量减少可能是引起受体后胰岛素抵抗的原因之一。