以高胰岛素原血症为主要表现的胰岛素瘤一例报告

胰岛素瘤是导致器质性低血糖症的主要病因之一，该病患者多表现为高胰岛素血症和低血糖，特别是在低血糖状态下出现血清胰岛素水平的不适当升高^[1,2]。目前临床上常通过测定血清免疫反应性胰岛素(IRI)水平对胰岛素瘤进行定性诊断。如果患者的血清IRI水平未见升高，则给确诊胰岛素瘤带来一定的困难。近期本科联合消化科、胰腺外科及病理科共同诊断     

丙型肝炎患者胰腺组织中HCV的检测

应用ＨＣＶ Ｃ３３ｃ单克隆抗体和免疫组化链霉菌抗生物素蛋白－过氧化酶连结法（Ｓ－Ｐ法）对２３例丙型肝炎患者尸解的胰、肝组织进行了丙型肝炎病毒检测，其中胰腺５例阳性（２１．７％），肝组织１４例阳性（６０．９％）。ＨＣＶＡｇ染色颗粒均见于细胞浆内，胰腺组织中的ＨＣＶＡｇ阳性细胞呈单个或簇状弥散分布，同时还在部分胰岛及导管上皮细胞内可见阳性表达。进而用地高辛素标记的ＨＣＶ ｃＤＮＡ探针，对其中９例做了在     

胰岛素原的基础和临床研究

本文综述了人胰岛素原的基本特性、测定方法及其与ＮＩＤＤＭ、ＩＤＤＭ、胰岛素瘤、家族性高胰岛素原血症以及心血管疾病的关系。     

胰腺内分泌肿瘤细胞成分的免疫组织化学观察及其对肿瘤起源的探讨

目的探讨胰腺内分泌肿瘤的生物学起源。方法应用链菌素亲生物素－过氧化物酶标免疫组织化学技术（Ｓ－Ｐ法）对５２例胰腺内分泌肿瘤（胰岛素瘤３２例，非功能性胰腺内分泌肿瘤２０例）瘤细胞内胰岛素、胰高血糖素、舒血管肠肽、生长抑素、胃泌素、Ｐ一物质、促肾上腺皮质激素、绒毛膜促性腺激素及５－羟色胺等９种激素或激素类物质的分布进行了观察。结果６５。５％（１３／２０）的非功能性胰腺内分泌肿瘤的细胞具有合成与低存激素的功能．３２．７％（１７／５２）胰腺内分泌肿瘤可含有分泌异位激素的细胞，６３．５％（３３／５２）的胰腺内分泌肿瘤是由多种内分泌细胞所构成。结论支持胰腺内分泌肿瘤是由胰腺内分泌于细胞起源的理论。     

血清瘦素水平与胰岛素原、真胰岛素及胰岛素敏感性的关系

目的　研究中国人群空腹瘦素水平与真胰岛素 (TI)、胰岛素原 (PI)、PI/TI比值及胰岛素敏感性之间的关系。方法　 90 2例非糖尿病者均系 2 0 0 0年接受糖尿病流行病学调查者。测定空腹瘦素、TI和PI浓度以及空腹及餐后 2h血糖。瘦素、TI及PI检测采用本室建立的特异的酶联免疫分析法 (ELISA)。胰岛素敏感性以HOMA胰岛素抵抗指数 (HOMA IR)评价。结果　血清瘦素水平女性高于男性。相关分析显示血清瘦素水平与空腹TI、PI及HOMA IR显著正相关 (男性 792例 ,r分别为0 345、0 2 36和 0 364 ;女性 1 1 0例 ,r分别为 0 574、0 375和 0 576 ,P <0 0 0 1 ) ,但与空腹血糖仅在男性呈弱相关 (r=0 1 5 ,P =0 0 1 5) ,与空腹PI/TI比值不相关。在调整年龄、体重指数 (BMI)和腰臀围比(WHR)后 ,尽管相关性减弱 ,瘦素水平仍然与TI、PI以及HOMA IR显著相关。结论　本组的血清瘦素浓度与TI、PI以及胰岛素抵抗显著正相关 ,且在一定程度上独立于肥胖和脂肪分布。瘦素水平高或瘦素抵抗的个体可能存在高胰岛素血症和胰岛素抵抗 ,提示其瘦素 胰岛素轴的调节异常。本研究未发现瘦素水平与空腹PI/TI比值的相关 ,提示瘦素可能与这一反映胰岛 β细胞的功能异常的标志无关。本研究揭示的高瘦素 高胰岛素血症或胰岛素抵抗之间的     

胰腺导管腺癌组织中WT1,IGF-IR表达与细胞凋亡的关系

目的:研究胰腺导管腺癌组织中WT1,IGF-IR的表达与细胞凋亡关系．方法:应用免疫组化技术检测WT1,IGF-IR在49例胰腺导管腺癌及15例正常胰腺组织中的表达,并应用TUNEL法检测细胞凋亡,计算凋亡指数(AI)．结果:WT1,IGF-IR在正常胰腺组织中的阳性表达率分别为26．67％(4／15)、40．00％(6／15);在胰腺导管腺癌组织中的阳性表达率分别为71．43％(35／49)、77．55％(38／49),两者在癌组织中的表达分别明显高于其在正常胰腺组织中的表达(P<0．05),且在癌组织中的表达呈正相关(r=0．385,P<0．05)．正常胰腺组织及癌组织中的AI分别为0．41±0．13、5．93±4．18,两者比较有显著性差异(P<0．05),癌组织中AI随组织分化程度的升高而升高．IGF-IR表达阳性组的AI显著低于阴性组(4．11±3．68 vs 12．21±5．67,P<0．01)．结论:胰腺导管腺癌组织中IGF-IR的高表达抑制细胞凋亡,WT1,IGF-IR的高表达以及细胞凋亡的减少可能在胰腺导管腺癌的发生发展中起重要作用．     

Ki-67在胰岛素瘤中的表达及其意义

胰岛素瘤是最常见的胰腺内分泌肿瘤。Ki-67作为一种细胞增殖标志，与多种肿瘤的分化、浸润、转移和预后密切相关。目的：研究Ki-67在胰岛素瘤中的表达情况。探讨其作为胰岛素瘤良恶性鉴别和预后判断标志物的可能性。方法：选取45例胰岛素瘤组织和9例配对瘤旁正常胰腺组织，以免疫组化方法检测Ki-67的表达。并分析其表达与胰岛素瘤临床病理特征的关系。结果：45例胰岛素瘤组织中18例Ki-67表达阳性，阳性率为40．0％，9例配对瘤旁正常胰腺组织均不表达Ki-67。5例（11．1％）胰岛素瘤组织Ki-67指数≥2％。除术前血糖〈2．8mmol／L者Ki-67表达阳性率显著低于术前血糖≥2．8mmol／L者（P=0．025）外，Ki-67表达阳性与否和Ki-67指数与胰岛素瘤的临床病理特征，包括性别、年龄、症状出现至确诊时间、肿瘤原发部位、大小、是否多发、良恶性、有无转移和术后是否治愈均不相关。结论：根据本研究结果尚不能确定Ki-67能作为鉴别胰岛素瘤良恶性和预后判断的标志物。     

胰腺导管腺癌组织中人表皮生长因子受体2的表达及临床意义

目的:探讨人表皮生长因子受体2(HER2)在PDAC组织中的表达及与PDAC患者预后的关系。方法:收集2001年1月至2012年12月间复旦大学附属华东医院病理科存档的109例PDAC组织石蜡标本和27例正常胰腺组织标本,采用免疫组织化学Envision二步法检测胰腺组织HER2蛋白的表达,根据Hercep Test评...     

Midkine在胰腺癌组织中的表达及临床意义

目的 探讨人胰腺癌组织中Midkine（MK）的表达及其与肿瘤细胞增殖的关系和意义。方法 免疫组织化学SP法检测49例胰腺癌、13例慢性胰腺炎及15例正常胰腺组织中MK和Ki67蛋白的表达。结果胰腺癌组织中MK和Ki67均高表达，阳性率分别为77．1％（35／49）、81．6％（40／49），二者的表达都与肿瘤组织学分级、临床分期和淋巴结转移有关（P〈0．05）。胰腺癌组织中Ki67表达显著高于慢性胰腺炎（3／13，P〈0．01）和正常胰腺组织（0／15，P〈0．01）。慢性胰腺炎和正常胰腺组织中未见MK阳性表达。胰腺癌组织中MK蛋白的表达与Ki67的表达呈正相关（r-0．4，P〈0．05）。结论 检测MK蛋白对于胰腺癌的诊断及与慢性胰腺炎的鉴别诊断具有参考价值。MK在胰腺癌中高表达可能与肿瘤的发生发展及细胞增殖密切相关。     

In vitro conversion of proinsulin to insulin by cathepsin B and role of C-peptide

Summary Cathepsin B, purified from isolated islets of Langerhans, when incubated with proinsulin underin vitro conditions could convert proinsulin to insulin and C-peptide, releasing free arginine and lysine. When C-peptide, prepared from rat pancreas, was added to the incubation system consisting of proinsulin and cathepsin B, it completely inhibited the conversion of proinsulin to insulin. Communication no. 2295 from the Central Drug Research Institute, Lucknow, India.     

高血压病患者的真胰岛素、胰岛素原水平及其与血压的关系

目的 探讨高血压病患的真胰岛素（TI）,胰岛素原（PI）水平及其与血压的关系,方法 测定非糖尿病的66例高血压病患及73例血压正常的收缩压（SBP）,舒张压（DBP）,血脂及口服葡萄糖耐量试验（OGTT）各点的血糖,血清TI和PI水平,TI及PI测定采用特异的单克隆抗体放大酶联免疫分析法（BA－ELISA）。结果 高血压病组在调整年龄,体重指数（BMI）和腰臂比（WHR）,其糖负荷后2h的PI及PI／TI水平显高于对照组（P＜0．05）,两而组间TI差异无统计学意义,单相关分析显SBP与空腹PI,2h PI及2h PI/TI 显相关,而BP仅与2h PI/TI显相关（P＜0．05）,仅在非肥胖组发现SBP与2hTI呈正相关（P＜0．05）,多因素回归分析显示2h PI独立于年龄,BMI,血糖和血脂等影响血压的混杂因素与SBP及高血压显相关。结论 本人群中高血压病患存在糖负荷后高PI血症,血清PI而非TI水平与高血压显正相关。     

Abnormal proinsulin/c-peptide ratio in juvenile diabetes

Summary B-cell function was studied in 20 diabetic children, with an age at onset of diabetes between 1–16 years (8.8 ± 4.0). Serum samples were taken before the first insulin injection and after 1, 3, 6, 9 and in a few patients after 18 months. At 3, 9, and 18 months the patients were also given a standardized breakfast load. Serum proinsulin, C-peptide, IRI and insulin antibodies (IgG) were determined. At onset 19 patients had measurable C-peptide (0.22 ± 0.17 pmol/ml; range 0.05–0.58). Proinsulin varied between 0.000–0.25 pmol/ml (0.069 ± 0.071) and at onset amounted to 31.3 ± 29.4 (0–100)% of C-peptide as compared to 3.3 ± 1.1 (1.7–6.6) in non-diabetics. A long partial remission was significantly correlated to a low proinsulin/C-peptide ratio at onset. In patients with low fasting proinsulin and no insulin antibodies, breakfast stimulation was accompanied by an increased proinsulin release at 3 and 9 months. The results suggest that abnormal proinsulin secretion is a feature of the ‘B-cell exhaustion’ complex in juvenile-onset diabetes.     

Insulin,proinsulin, proinsulin:insulin ratio,and the risk of developing type 2 diabetes mellitus in women

PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin:insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (< or =4.0 pmol/L, 4.01 to 6.99 pmol/L, > or =7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (> or =7.0 pmol/L vs. < or =4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin:insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A(1c) level < or =6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin:insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women.     

Proportional proinsulin responses in first-degree relatives of patients with type 2 diabetes mellitus

Elevated fasting proinsulin immunoreactive material (PIM) has previously been found in patients with type 2 (non-insulin-dependent) diabetes mellitus. It is not known whether this is a genetic trait or whether it is related to the manifestation of type 2 diabetes. Neither is it clear whether the raised fasting insulin immunoreactivity previously observed in first-degree relatives of patients with type 2 diabetes is due to raised PIM. Furthermore, it has not been investigated whether first-degree relatives have altered PIM responses to different secretagogoues. To study this, PIM, insulin and C-peptide were measured in patients with type 2 diabetes, in their first-degree relatives and in healthy control subjects in the fasting state and in relatives and controls during a hyperglycemic clamp. At the end of the hyperglycemic clamp, 0.5 mg of glucagon was given intravenously to stress the beta cells further. Fasting PIM concentrations were significantly higher in patients with type 2 diabetes (P<0.05). These patients did not have significantly elevated fasting insulin levels when corrected for PIM. In the relatives, fasting insulin concentrations were elevated but PIM levels were normal suggesting that the increase in fasting insulin concentrations reflected an increase in true insulin. The incremental PIM, insulin and C-peptide responses to glucose and glucagon in the relatives were not different from those in the controls. We conclude that elevated fasting PIM levels in patients with type 2 diabetes seem not to be a genetic trait. First-degree relatives of patients with type 2 diabetes are truly hyperinsulinemic in the fasting state, and they have proportional PIM, insulin and C-peptide responses to glucose and glucagon.     

Plasma proinsulin,C-peptide and insulin in diagnostic suppression tests for insulinomas

Summary The value of plasma insulin, human C-peptide and proinsulin estimation in the diagnosis of 15 insulinomas has been investigated. Measurement of plasma proinsulin in an overnight fasting sample diagnosed all the insulinomas studied, irrespective of the plasma glucose. Patients with insulinomas had plasma proinsulin in the range 0.04–4.2 pmol/l and normal values were less than 0.01 pmol/ml. If hypoglycaemia was present, an inappropriately raised plasma immunoreactive insulin (including proinsulin) was diagnostic, but this assay was of little assistance if the plasma glucose was normal. Hypoglycaemia was induced with fish insulin in twelve patients with insulinomas and eight normal subjects. Using an antiserum which did not detect fish insulin, but cross-reacted with human proinsulin, the endogenous immunoreactive insulin was suppressed in the normal subjects, but all insulinoma patients had impaired suppression. Assay of plasma human C-peptide, or of the combined immunoreactive C-peptide and proinsulin, discriminated less well and did not clearly diagnose three insulinomas which secreted proinsulin rather than insulin and C-peptide. Plasma human proinsulin values during induced hypoglycaemia gave excellent discrimination and should detect insulinomas irrespective of their degree of histological differentiation. The assay of plasma human proinsulin allows a suppression test to be performed with hypoglycaemia induced by any type of insulin. A raised plasma proinsulin in proportion to C-peptide suggests an undifferentiated insulinoma, which may be more likely to be malignant.     

肥胖青少年血清瘦素、胰岛素和胰岛素原水平的变化

目的　检测肥胖青少年血清瘦素、胰岛素、胰岛素原水平的变化 ,探讨青少年肥胖与代谢综合征的关系。方法　从年龄 14～ 16岁的 2 2 17例学生中筛选出体重指数 (BMI)≥ 2 5kg/m2 的肥胖学生 (肥胖组 ) 198例 ,BMI在 18 5～ 2 3 0kg/m2 之间的体重正常学生 (正常组 ) 78例 ,用放射免疫方法测定血清瘦素、胰岛素和胰岛素原水平 ,同时测定血糖及血脂水平 ,比较两组间差异。结果　血清瘦素水平女生明显高于同龄男生 [(18 5 3± 1 4 1) μg/L比 (6 33± 1 79) μg/L]。肥胖组血清瘦素、胰岛素和胰岛素原水平均高于同龄体重正常者 [分别为 (19 94± 1 91) μg/L比 (11 2 7± 2 0 4 ) μg/L ,(15 34± 1 6 6 ) μIU/L比 (13 17± 1 4 3) μIU/L ,(16 19± 1 6 4 )pmol/L比 (11 79± 1 70 )pmol/L ],血糖、甘油三酯 (TG)和高密度脂蛋白胆固醇 (HDL C)水平虽然在正常范围内 ,但肥胖者血糖和TG水平高于同龄体重正常者 [分别为 (4 6 3± 0 5 0 )mmol/L比 (4 13± 0 33)mmol/L ,(1 2 0± 0 5 6 )mmol/L比 (0 90±0 32 )mmol/L],HDL C水平低于同龄体重正常者 [(1 14± 0 2 4 )mmol/L比 (1 38± 0 2 6 )mmol/L]。结论　肥胖青少年可能存在瘦素抵抗、胰岛素抵抗及潜在的糖代谢和脂代谢异常等代谢综合征改变 ,     

不同糖耐量个体血清瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性的关系探讨

目的　研究不同糖耐量人群空腹瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性之间的关系。方法　用放射免疫法测量 5 4例正常糖耐量 (NGT)、33例糖耐量低减 (IGT)、4 7例新发 2型糖尿病 (DM )的空腹瘦素水平、口服葡萄糖耐量试验 (OGTT) 0、1/2、1、2h的特异胰岛素 (SI)和胰岛素原 (PI)。结果　 (1)多元逐步回归分析显示 ,性别、体重指数 (BMI)、胰岛素敏感性指数是影响空腹瘦素水平最重要的因素 (校正的R2 分别为 0 .2 5 1、0 .4 19、0 .4 38,P值分别为 <0 .0 0 1、<0 .0 0 1、<0 .0 5 ) ;空腹血清瘦素水平与OGTT各时间点PI、SI、PI/SI值无相关性。 (2 )在校正性别、BMI等影响因素后 ,空腹血清瘦素水平在不同糖耐量组差异无显著性 ;DM组OGTT各时间点PI/SI值明显高于IGT组和NGT组 (P <0 .0 1) ;胰岛素敏感性 (ISI)为NGT组 >IGT组 >DM组 (P <0 .0 0 1)。结论　在测定特异胰岛素、胰岛素原时 ,血清瘦素水平除了与性别、BMI相关外 ,尚与胰岛素敏感性 (按SI水平计算 )相关 ;不同糖耐量状态对血清瘦素水平无明显影响 ;DM组存在胰岛素不敏感、PI/SI失调     

胰岛素原、真胰岛素与冠心病危险因素的关系

目的 探讨胰岛素原（PI）,真胰岛素（TI）是否与冠心病危险因素相关。方法 采用BAELISA法测定119例入选口服葡萄糖耐量试验（OGTT）各时相的PI,TI水平,并与冠心病危险因素及其数目作相关分析。结果 空腹及糖负荷2h PI,TI与冠心病危险因素数目（r=0.19-0.33), 体重指数（BMI）(r=0.23-0.41)及WHR（r=0.32-0.51)呈正相冯,而与HDL－C（r=0.22-0.30),负相关;空腹PI及2h糖同PI,TI高血压（r=0.18-0.20),葡萄糖耐量减低（IGT）（r=0.13-0.34),TG(r=0./32-0.33)和尿酸（r=0.27-0.36)呈正相关,空腹及2h PI与apoB(r=0.26)呈正相关,2h PI与TC（r=0.21)及家庭史（r=0.21)呈正相关;经校正年龄,性别,BMI,WHR（腰臂比值）,空腹及2h血糖后,TI与血脂的关系消失,PI与血脂的关系减弱;空腹PI与TG（r=0.32),apoB(r=0.19)及尿酸（r=0.22)呈正相关,2h PI与apoB(r=0.27)及尿酸（r=0.20)正相关,与HDL－C（r=-0.21)呈负相关,多元逐步回归分析法亦显示PI与血脂的关系比TI更密切,结论 PI,TI与冠心病危险因素有明显关系,而且PI比TI与冠心病危险因素的关系更密切。