2型糖尿病一级亲属不同糖耐量者第一时相胰岛素分泌功能的变化

目的：探讨胰岛素分泌功能和胰岛素抵抗（IR）在2型糖尿病（T2DM）发生、发展中的作用。 方法： T2DM一级亲属正常糖耐量（NGT+）组32例，T2DM一级亲属糖耐量异常（IGT+）组36例，新诊断的T2DM组35例，计算各组的第一时相胰岛素分泌功能指数（AIR3-5）及胰岛素敏感性指数（SIM），与无糖尿病家族史的正常糖耐量（NGT-）组（38例）比较。 结果： T2DM一级亲属T2DM组、IGT+和NGT+组AIR3-5均低于NGT-组（P值分别为<0.01、<0.01、＜0.05）；T2DM组和IGT+组SIM均低于NGT-组（均P<0.01），而NGT+组SIM值与NGT-组比较无统计学差异（P>0.05）。结论： 胰岛素分泌功能缺陷可能是T2DM发病的始动因素。当发展为IGT及T2DM时，胰岛素分泌功能进一步降低，并伴有胰岛素敏感性的降低。     

不同病程非胰岛素依赖型糖尿病人的胰岛素分泌反应

磺脲类药物继发性失效是非胰岛素依赖型糖尿病(NIDDM)治疗过程中较难克服的问题,随着(?)程的延长,其发生率有增多趋势,为了解不同病程NIDDM发生继发性失效的规律,我们分析了283例未使用过胰岛素的NIDDM胰岛素分泌曲线,以图对其治疗有所帮助。 对象和方法 一、对象:在我院住院的符合WHO诊断标准的NIDDM 283人(男157,女126),全部病例均末使用过胰岛素,年龄36～77岁,平均55.38±11.74岁,病程1～32年。按病程<3年,3～6年,6～9年,>9年分为4组。 二、方法:受试者隔夜禁食12小时,进食馒头100克,于进食前及进食后0.5、1、2、3小时抽血测定胰岛素及C肽值,胰岛素及C肽测定均用RIA法,试剂盒由中国原子能研究院提供,仪器用北京核仪器厂生产的FT-630型微机多探头放免测定仪。显著性检验用t检验。 结果 不同病程的NIDDM不同时相的胰岛素及C肽结果分别见表1和表2。     

2型糖尿病患者的肥胖子女与非肥胖子女胰岛素分泌功能的对比观察

目的 :探讨 2型糖尿病 (DM)患者的肥胖子女与非肥胖子女的胰岛素分泌功能的 6个参数水平的变化。方法 :以 2型糖尿病患者的 2 3名非肥胖子女为A组 ,18名肥胖子女为B组 ,对照组用 2 7名健康体检者 ,行简化的口服葡萄糖耐量试验 (OGTT) ,测空腹血糖和胰岛素 ,服糖后 2h血糖和胰岛素 ,应用稳态模式胰岛素抵抗指标 (HOMA -IR)作为胰岛素抵抗指标 ,用稳态模式胰岛 β细胞功能指数 (HBCI)作为胰岛素分泌指标 ,对三组的这些指标进行对比分析。结果 :与对照组比较 ,A组空腹血糖相对升高 (P <0 0 5 ) ,HBCI降低 (P <0 0 5 ) ,B组空腹血糖升高 (P <0 0 5 ) ,服糖后 2h血糖升高 (P <0 0 5 ) ,HBCI降低 (P <0 0 1) ,HOMA -IR升高(P <0 0 5 )。结论 :2型DM患者的非肥胖子女在出现糖耐量减低前存在胰岛素分泌功能减退 ,肥胖子女减退更明显。     

胰岛素分泌细胞的来源

糖尿病是严重危害人类健康的重大疾病之一。且近年来此病的发病率星上升趋势,目前治疗该病的有效方法是胰岛索治疗,给社会和家庭带来了沉重的负担。胰岛移植虽是治疗此病的有效手段,但面临胰岛供体匮乏,免疫排斥以及使用免疫抑制剂给病人带来痛苦等困难。能找到可以避免上述困难又能有效分泌胰岛素的细胞将给亿万糖尿病病人带来福音。     

不同培养时间对NIT-1细胞胰岛素分泌及相关基因表达的影响

目的：研究体外生理浓度葡萄糖培养胰岛β细胞株NIT-1细胞在不同时间出现的功能变化及其可能机制。方法：观察5.6 mmol/L葡萄糖浓度的DMEM完全培养基培养的NIT-1细胞在 8周培养时间内细胞的形态变化；胰岛素免疫细胞化学染色；应用放射免疫法测定8周葡萄糖刺激的胰岛素分泌水平；并以RT-PCR半定量测定各基因Insulin、Glut2、GK、PDX-1、NeuroD1、Pax4、Pax6 mRNA表达水平变化。结果：（1）传代培养过程中细胞生长良好呈多边形，不同培养时间的NIT-1细胞形态无显著差异；（2）胰岛素免疫细胞化学染色示GSIS组胞浆染色阳性，呈淡黄褐色；（3）1-8周每周测定的葡萄糖刺激的胰岛素分泌（GSIS）与第1周数据比较，显示胰岛细胞分泌功能改变差异显著（P<0.05）；（4）1-8周每周测定的胰岛素基因、PDX-1基因、GK基因、Glut2基因、NeuroD1基因和Pax6基因mRNA的表达与第1周比较，显示基因mRNA的改变差异显著（P<0.05）； Pax4基因mRNA的改变无显著差异（P>0.05）。结论: 生理浓度葡萄糖培养的NIT-1细胞的葡萄糖刺激的胰岛素分泌功能随体外培养时间的延长呈逐步下降趋势；这可能与维持β细胞功能有关的基因Insulin、PDX-1、 GK、Glut2、NeuroD1 和 Pax6 表达下降有关。     

生物钟节律紊乱影响糖尿病小鼠糖代谢及胰岛素分泌的实验研究

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。     

心理应激对血糖及胰岛素分泌的影响

目的了解心理应激对胰岛素分泌及血糖的影响.方法以健康男大学生为研究对象,采用速算作业使学生产生心理应激,测定应激前后空腹血糖及血清胰岛素值.结果心理应激后血糖较应激前明显增加(t=3.81,p<0.001),血清胰岛素浓度及胰岛素敏感指数较应激前降低(t=4.23,p<0.001);肥胖学生应激所致的血糖增加值较体型正常学生大;应激所致的血糖改变量与胰岛素的改变量呈负相关(r=-0.308,p<0.05).结论心理应激可使健康学生血糖增加;肥胖可增大心理应激的升血糖作用.     

Tubacin对β细胞葡萄糖刺激胰岛素分泌的影响

目的：观察去乙酰化酶HDAC6特异性抑制剂Tubacin对MIN6细胞胰岛素分泌的影响,并探讨其可能机制。方法：用RT－PCR检测去乙酰化酶家族成员在MIN6细胞的表达,用免疫荧光技术观察HDAC6在小鼠胰岛和MIN6细胞内的定位;分别在5．6mmol／L和25mmol／L葡萄糖的DMEM中加和不加10μmol／LTubacin,用其处理MIN6细胞24h,收集上清,ELISA检测胰岛素浓度。同时用MTT法检测Tubacin对MIN6细胞活力的影响,RT－PCR检测上述处理条件下Insulin基因的表达情况。以Westernblot和免疫荧光技术检测Tubacin对MIN6细胞骨架蛋白α－tubulin乙酰化水平的影响。结果：MIN6细胞中各乙酰化酶家族成员mRNA的表达水平相差较大,其中HDAC6表达相对较高。HDAC6主要表达于小鼠胰岛B细胞及MIN6细胞胞浆中。在5．6imnol／L和25mmol／L葡萄糖条件下,Tubaein处理24h可以显著抑制胰岛素分泌,但不影响MIN6细胞活力。同时,在5．6mmol／L葡萄糖存在条件下Tubacin不影响胰岛素基因表达,在25mmol／L葡萄糖存在条件下Tubacin可轻度上调胰岛素基因表达。Westernblot和免疫荧光结果发现,Tubacin抑制胰岛素分泌的同时伴有α—tubulin乙酰化水平增加。结论：HDAC6抑制剂Tubacin可能通过增加MIN6细胞d．tubulin乙酰化水平,改变细胞骨架的活动度而抑制胰岛素分泌。     

中药及天然药物对改善2型糖尿病胰岛素抵抗的研究进展

2型糖尿病是由于绝对或相对的胰岛素分泌不足和靶组织细胞对胰岛素敏感性降低,而引起的糖、脂肪、蛋白质及水电解质等一系列代谢紊乱所致的一种内分泌代谢性疾病,占糖尿病病人的90％以上。在2型糖尿病发病过程中,胰岛素抵抗（Insulin Resistance,IR）是关键环节,胰岛素抵抗主要是指胰岛素作用的受体前、受体及受体后缺陷,使胰岛素介导下的肌肉和脂肪组织摄取葡萄糖的能力降低,同时肝糖原生成增加,     

The impact of obesity on diabetes mellitus and the role of bariatric surgery

Over 1.5 billion adults worldwide are classified as either overweight or obese, with rates continuing to increase. Obese individuals are at an increased risk for multiple disease processes, particularly type-2 diabetes mellitus (T2DM). Obesity has a strong association with insulin resistance, hyperinsulinemia and glucose intolerance. Adiposity, both subcutaneous and visceral, has been proposed to contribute to insulin resistance, eventually leading to T2DM. Strong evidence exists, in both genders, for the increased glucose intolerance and incidence of T2DM with increasing weight gain. Conversely, weight loss is associated with improvement of glycemic control, insulin resistance and T2DM. Bariatric surgery has risen as a therapeutic option that provides exceptional reduction in overall weight and resolution of T2DM. However, bariatric surgery serves as one component of a multifaceted weight management strategy that is required for long-term success.     

Serum testosterone in Nigerian men with type 2 diabetes mellitus and its relationship with insulin sensitivity and glycemic control

BackgroundThere is increasing evidence that testosterone deficiency has key associations with insulin sensitivity and glycemic control. Its presence may therefore contribute to and/or exacerbate clinical disease in men with type 2 diabetes mellitus (T2DM). This study sought to determine the frequency of low free testosterone and explore its relationship with, insulin sensitivity and glycemic control among Nigerian men with T2DM.MethodsOne hundred and four men with type 2 DM and one hundred and one apparently healthy non-diabetic men matched for age, were recruited into the study Socio-demographic data, anthropometric measurements and blood samples were obtained for measurement of serum total testosterone (TT), sex hormone binding globulin (SHBG), fasting plasma insulin, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting lipid profile in all the subjects. Insulin sensitivity (%IS) and free testosterone (CFT) were then calculated.ResultsThe median CFT for men with T2DM was significantly lower than that of non-diabetic controls (0.17 nmol/L vs 0.58 nmol/L respectively; P < 0.001). 52.9% of men with T2DM had low CFT, as compared with 21.4% amongst the non-diabetic controls; P < 0.001.Among men with T2DM, those with lower CFT had significantly lower median % S and higher mean HbA1c than those with normal CFT (37.0% versus 63.0%; P = 0.021 and 7.79 (2.03) % versus 7.02 (1.94) %; P = 0.038 respectively]. HbA1c had significant negative correlations with both CFT (correlation coefficient: ?0.239 (P < 0.05) and TT (correlation coefficient: 0.354; P < 0.01.There was no significant difference in serum lipids when T2DM men with low serum CFT were compared with T2DM men with normal serum CFT levels.ConclusionWe conclude that low serum testosterone is common among men with T2DM and has a significant association with glycemic control (HbA1c) and insulin sensitivity.     

Cholecystokinin (CCK8) regulates glucagon,insulin, and somatostatin secretion from isolated rat pancreatic islets: interaction with glucose

The effect of CCK₈ on glucagon, insulin and somatostatin release and its interaction with glucose was studied in freshly isolated rat pancreatic islets. While glucose alone inhibited glucagon secretion [half-maximal effect (EC₅₀)=4.6 mM], glucose in the presence of 10 nM CCK₈ increased glucagon release (EC₅₀=6.9 mM). This effect of CCK₈ was dose-dependent at 11.1 mM glucose (EC₅₀=1.0 nM). The dose-response curve for glucose on insulin secretion was shifted to the left by 10 nM CCK₈; the EC₅₀ of glucose was 11.6 and 9.3 mM in the absence and presence of CCK₈, respectively. Glucose alone enhanced somatostatin release; this glucose-induced release was further increased by 10 nM CCK₈. Our data indicate that first, CCK₈ is able to reverse the inhibitory effect of glucose on glucagon secretion, second, CCK₈ sensitizes the beta cell to the insulinotropic effect of glucose, and third, CCK₈ enhances the effect of glucose on somatostatin release.     

Suppression of food intake by intragastric glucose in rats with impaired glucose tolerance

Three experiments were performed to examine the relationship between impaired glucose tolerance and food intake. In the first experiment, normal rats that were given long-term insulin treatment, which was then withdrawn, ate less than controls when refed after food deprivation. Despite reduced intakes, rats previously treated with insulin became more hyperglycemic than controls during refeeding. In the second experiment, intragastric glucose injections reduced food intakes to a similar degree in control rats and in rats experiencing insulin withdrawal even though glucose loading produced a much greater increase in plasma glucose level in previously insulin-treated rats. In the third experiment, intragastric loads of a glucose polymer, Polycose, reduced food intake to the same degree in normal rats and in streptozotocin-diabetic rats both two and sixteen days after insulin withdrawal when diabetic rats were, respectively, hypo- and hyperphagic. The results show that impaired glucose tolerance does not appreciably alter the suppressive effects of glucose loading on food intake. Other effects of glucose administration, besides those on insulin-dependent glucose utilization, appear to reduce food intake after glucose loading.     

不同治疗方式对新发2型糖尿病患者胰岛β细胞功能及胰岛素抵抗的影响

目的 比较采用胰岛素治疗(INS)与口服降糖药物治疗(OHA)等不同治疗方式对新发2型糖尿病(T2DM)患者胰岛β细胞功能及胰岛素抵抗的影响,推断新发T2DM的最佳治疗方案.方法 将62例新发T2DM患者随机分为胰岛素治疗组(INS组)和口服降糖药物组(OHA组).OHA组首选磺脲类或二甲双胍,或二者合用,疗效欠佳时增加噻唑烷二酮类,一般为2药或3药合用.两组治疗期均为3个月.每组根据血糖调整剂量,目标为空腹血糖(FBG)＜6.0 mmol/L,餐后2h血糖(2hPG)＜8.0mmol/L.观察两组治疗前后FBG、2h PG、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、空腹及餐后2hC肽(FCP、2hCP)水平的变化;用稳态模型(Homa)计算胰岛β细胞功能指数(Homaβ=20×FINS/(FBG-3.5)和胰岛素抵抗指数[HomaIR=(FBG×FINS)/22.5].用治疗后CP、Homaβ、HomaIR等相关指标进行组间比较,以评价胰岛β细胞功能及外周胰岛素抵抗的变化.结果 :(1)治疗后,两组患者FBG、2hPG、HbA1C水平较治疗前均有明显下降(P＜0.01),而在两组间比较差异无统计学意义;(2)治疗后,INS组患者FINS、FCP、2hCP、Homaβ较治疗前升高(P＜0.05),OHA组则无明显变化(P＞0.05),两组间比较差异有统计学意义(P＜0.05);(3)治疗后,INS组患者HomaIR较治疗前有明显下降(P＜0.05),OHA组仅略有下降,两组间比较差异有统计学意义(P＜0.05).结论 早期应用胰岛素治疗可以改善新发T2DM患者胰岛β细胞分泌功能及外周胰岛素抵抗.与OHA相比,INS能更好地保护患者的胰岛B细胞功能.     

Effects of unilateral nigrostriatal dopamine depletion on peripheral glucose tolerance and insulin signaling in middle aged rats

Clinical studies indicate an increased incidence of impaired glucose tolerance in individuals with Parkinson's disease (PD). The mechanisms that underlie this co-morbidity are currently unknown. The purpose of this study was to analyze peripheral glucose tolerance following severe unilateral nigrostriatal dopamine (DA) depletion, and to determine whether central and peripheral insulin signaling was affected in the 6-hydroxydopamine (6-OHDA) middle-aged rat model of PD. Although serum insulin levels differed significantly between the 6-OHDA and sham groups over the course of a glucose tolerance test six weeks post-lesion, no significant effect on glucose tolerance or insulin signaling in skeletal muscle was observed. In contrast, markers of striatal insulin resistance were evident in the rats. These data suggest that while 6-OHDA may affect serum insulin levels and striatal insulin signaling, the unilateral 6-OHDA lesion model does not induce glucose intolerance or peripheral insulin resistance, at least at the six-week post-lesion timepoint.     

Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion

Summary It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 ± 6.8 mg/day for 12 ± 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 ± 0.61 to 5.77 ± 0.78 mmol/1 and from 5.61 ±2.05 to 7.55 ± 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A_1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5 ± 2.6 to 12.1 ± 5.1 mU/1 (P<0.01) and from 71.3±52.1 to 101.4±50.7 mU/1 (P<0.02), respectively. A direct relationship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.Abbreviations AUC area under the curve - GH growth hormone - PRL prolactin Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

营养物质调节胰岛素分泌机制的研究进展

胰岛素是人体内唯一起到降低血糖功能的重要激素.它调节机体血糖维持稳定,促进代谢,调节细胞的分裂分化和生长发育.胰岛素分泌不足或分泌功能障碍都将引起机体的糖代谢紊乱,从而引起糖尿病.该文简述营养物质,即糖、脂肪酸和多肽对胰岛素分泌的调节机制,并对可能影响胰岛素分泌的研究进行进一步展望.     

Impact of diabetes,obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases

Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.