水通道蛋白7与胰岛素分泌和胰岛素抵抗的关系

正水通道蛋白(AQPs)是一类介导水跨细胞膜转运的膜蛋白[1],迄今已在哺乳动物中共发现了13种AQPS(AQP0~12)[2]。依据AQPS的通透性,研究者将其分为AQPS、水甘油通道蛋白和超AQPS 3个亚族。其中,AQPS仅能对水进行高度选择性转运,水甘油通道蛋白除对水具有通透性以外,还可介导甘油、尿素等小分子的跨膜运输,而超AQPS的功能还不清楚。AQP7属于水甘油通道蛋白一族,其在维持     

中国人糖耐量异常与胰岛素抵抗和胰岛素分泌

研究胰岛素抵抗和胰岛分泌缺陷与中国人糖耐量变化的关系。方法对４６６例（正常体重１８９例,超重／肥胖２７７例）正常糖耐量（ＮＧＴ）、糖耐量减退／空腹血糖减损（ＩＧＴ／ＩＦＧ）、２型糖尿病（ＤＭ）患者,用稳态模式评估法评价胰岛素抵抗及胰岛β细胞基础功能（ＨＯＭＡ－βｃｅｌｌ）并用糖负荷３０分钟净增胰鸟争增葡萄糖（△ｉ３０／△Ｇ３０）比值评价早期胰 岛素分泌反应。结果校正年龄,性别、体重指数（ＢＭＩ）、     

NIDDM患者中胰岛素分泌与胰腺外分泌功能关系的初步探讨

为了探讨NIDDM患者中的胰腺外分泌功能状态及与胰岛素分泌之间的关系,我们应用馒头餐胰岛素释放试验和BT-PABA试验为指标,对81例NIDDM患者进行了初步研究。 一、对象:81例NIDDM均符合WHO建议的糖尿病诊断标准。男43例,年龄54.14±9.30岁;女38例,年龄53.42±7.41岁。病程4.21±3.76年(2个月～21年)。     

新型胰岛素分泌模式调节剂——那格列奈

控制2型糖尿病（T2DM）的最终目的是保存胰岛β细胞。因为早在血糖升高前15～20年，胰岛β细胞分泌胰岛素的能力巳经丧失50％～70％，为此，大多数抗糖尿病（DM）药物需长期服用，随着时间的推移，β细胞功能会逐渐丧失，使血糖控制达标越来越困难，故临床只关注血糖控制是不够的，治疗的目标应是改变糖尿病的自然病程，长期保护β细胞。正如国际胰岛素分泌研究组主席Cerasi教授一言以蔽之：胰岛素生成，胰岛素分泌及2型糖尿病：问题的核心在于β细胞。     

胰岛素脉冲样分泌的机制及临床意义

胰岛素的分泌呈脉冲样模式,其中包括慢速脉冲和快速脉冲两种模式,本文就它们的特点、机制、临床意义作一综述。     

胰岛素脉冲式分泌及其临床意义

生理状态下胰岛素分泌呈现脉冲方式,参与其分泌调节的途径一是葡萄糖调节,即K_(ATP)通道依赖的触发通路;二是非K_(ATP)通道依赖的扩大效应通路,两条途径协调作用。其调节机制目前认为与Ca~(2+)浓度的变化规律相关,同时一些神经体液因子也参与了脉冲式分泌的体内调节。而2型糖尿病者的脉冲分泌出现异常,予以减轻体重、磺脲类药物、胰升糖素样肽-1等干预,可以改善胰岛素的脉冲式分泌。     

2型糖尿病家系成员中的胰岛素抵抗与胰岛β—细胞功能状态的研究

目的研究胰岛素抵抗及胰岛紊分泌功能在2型糖尿病(DM)发生、发展中的作用.方法在2型DM家系成员中,对已诊断DM者按病程中位数分组,病程≤4年组153例,＜4年组129例.经口服葡萄糖耐量试验(OGTT),按1999年WHO糖尿病诊断标准,新诊断DM组72例.非DM者按HbAlc分组,HbAlc≤5.5%组78例,HbAlc＜5.5%组110例,计算各组HOMA模型胰岛素抵抗指数(HOMAIR)、β细胞功能指数(HOMAβ)及胰岛素敏感性指数(ISI),与无DM家族史的正常人98例比较.结果除HbAlc≤5.5%组外,家系各组HOMAIR均值高于正常对照,差异有显著性(P＜0.01).家系非DM两组HOMAβ高于正常对照(P＜0.01),DM各组HOMAβ低于正常对照(P＜0.01).结论北京地区2型DM家系中非DM一级亲属的胰岛素抵抗及糖耐量异常可能继发于胰岛素分泌功能异常增高,胰岛素分泌功能降低和胰岛素抵抗是发生糖尿病的主要机制.     

中国新诊断2型糖尿病胰岛素分泌和胰岛素抵抗特点调查

目的 研究中国新诊断2型糖尿病患者胰岛素分泌功能(IS)及胰岛素抵抗(IR)状况.方法 对405例新诊断2型糖尿病患者和40名糖耐量正常者(对照组)测量身高、体重;行口服葡萄糖耐量试验(OGTT)及胰岛素释放试验.按空腹血糖(FPG)水平分为4组,与对照组比较.93例FPG≥8.3mmol/L者应用格列齐特(达美康)缓释片进行干预治疗1～3个月,血糖达标后重复OGTT并计算干预后的IR及IS.结果 (1)随着FPG水平的升高,糖尿病各组IR、IS逐级恶化:在FPG≥9.7mmol/L组,胰岛素敏感性为正常组的30%,IS仅为正常组的5%;(2)在FPG<9mmol/L组,IR能解释70%的血糖水平变化,而在FPG高于≥9mmol/L组,IS能解释60%的血糖变化;(3)格列齐特缓释片干预治疗IR及IS有了显著的改善.结论 新诊断2型糖尿病的IR及IS随空腹血糖升高而恶化,但是IS恶化更为严重;这种双重恶化在高血糖状态得到纠正后在相当程度上是可逆的.     

Pancreas size and insulin secretion: lack of association in non-diabetic subjects

Both type 1 and type 2 diabetes mellitus are associated with reduced pancreatic size. This could be caused by insulinopenia with loss of a trophic insulin effect and/or other factors associated with a diabetic state. To investigate the role of long-term moderate insulinemia per se, we compared the pancreatic size in healthy subjects with documented low (n=5) and high (n=5) insulin secretion. Insulin responses to a glucose clamp (11 mM) procedure were threefold higher in the high insulin responders (HIR) than low insulin responders (LIR). Age, body mass index (BMI), and blood glucose were similar between groups. Computed tomography showed no difference in total pancreatic size (total pancreas volume 84.8±29.4 ml in LIR, 79.8±8.4 ml in HIR; NS) nor in the size of various parts (caput, corpus, or cauda). We conclude that moderate hypoinsulinemia of long duration does not affect the pancreatic size.     

初发单纯空腹高血糖和(或)单纯餐后高血糖型糖尿病的代谢特征

目的评估单纯空腹高血糖型糖尿病(IFH),单纯餐后高血糖型糖尿病(IPH)及空腹合并餐后高血糖型糖尿病(FPH)的临床特点和胰岛素分泌及胰岛素敏感性的特征。方法2004至2005年瑞金医院内分泌门诊初诊糖尿病患者704例,据75g葡萄糖耐量试验分为:(1)IFH 81例;(2)IPH 147例; (3)FPH 476例。比较各组的胰岛素分泌及胰岛素敏感性指标。结果3组患者的年龄,体重指数,腰围及血压的差别无统计学意义。空腹胰岛素(O min)3组差异无统计学意义,30、60 min胰岛素FPH低于其他两组,120 min胰岛素IPH高于其他两组(均P＜0．05)。FPH组较IFH和IPH组有显著的早期相胰岛素分泌缺陷;IPH组和FPH组较IFH组的胰岛素敏感性降低。结论β细胞分泌缺陷和胰岛素抵抗均是从IFH向FPH进展的重要因素,而在IPH向FPH进展的过程中,β细胞的胰岛素分泌缺陷可能起到关键性的作用。     

有2型糖尿病家族史的初诊糖尿病患者胰岛素第一和第二时相分泌的异常

采用精氨酸刺激法和OGTT法观察初诊糖尿病患者胰岛素第一和第二时相分泌的变化。结果提示 ,有糖尿病家族史患者存在胰岛素第一时相和早期分泌功能异常。     

Oestrogens and insulin secretion

There is a persistent perception that oestrogens have an adverse effect on carbohydrate metabolism. It might therefore be expected that their use would result in a corresponding increase in the incidence of diabetes. Recent evidence from clinical trials suggesting that women on postmenopausal oestrogen hormone replacement therapy (HRT) have a reduced incidence of type 2 diabetes therefore appears paradoxical. Short-term supraphysiological oestrogen administration has an adverse effect on glucose tolerance, resulting from suppression of first-phase insulin secretion and increased insulin resistance. Oestrogen-induced increases in glucocorticoid activity could account for these effects. Oestrogen-induced deterioration in glucose tolerance is, however, accompanied by a reduction in fasting glucose, an effect that could be accounted for by glucagon antagonism. These short-term effects contrast with long-term preservation of insulin secretion and glucose homeostasis by oestrogens. In animal studies, ovariectomy is associated with decreased insulin secretion and increased risk of diabetes, whereas oestrogen administration protects against diabetes and increases the insulin response to glucose. The mechanism is uncertain, but direct effects on the pancreas via steroid receptors or indirect effects via oestrogen-induced glucagon antagonism and subclinical increases in glucocorticoids and growth hormone could all contribute. Recent evidence that HRT increases the risk of cardiovascular disease suggests that it should not be used for the prevention of diabetes, but the mechanism responsible for this benefit merits further investigation and might lead to new therapies.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

评估胰岛素分泌及胰岛素敏感性选择降糖药物的临床多中心研究

目的评价糖尿病病理生理变化对新诊断的2型糖尿病患者治疗的指导意义。方法按照精氨酸刺激试验的结果，将322例新诊断2型糖尿病患者分为一相胰岛素分泌正常组和低下组，将前者随机分配至瑞格列奈、罗格列酮及二甲双胍治疗组，后者随机分配至瑞格列奈、罗格列酮及格列吡嗪治疗组。结果（1）各药物治疗组，用药后3个月、6个月的空腹血糖、餐后2h血糖及HbA1C均较基线明显降低（均P〈0．01）。治疗后6个月HbA1C控制理想的总体达标率为63．5％。（2）在一相胰岛素分泌正常组，罗格列酮治疗后血糖校正后的精氨酸试验胰岛素曲线下面积（AUC）明显增加，胰岛素原显著减少（P〈0．01），二甲双胍治疗后胰岛素抵抗指数（HOMA—IR）较基线显著降低（P〈0．05）。（3）在一相胰岛素分泌低下组，瑞格列奈或格列吡嗪治疗后的精氨酸试验的2、4、6min真胰岛素均值与空腹真胰岛素的差值（△TI）、血糖校正后精氨酸试验的结果（ATI／PG）、AUC及真胰岛素（TI）明显增高（P〈0．05或P〈0．01），罗格列酮组治疗后的ATI／PG与AUC显著增加，而HOMA—IR及胰岛素原较治疗前明显减少（均P〈0．01）。结论（1）基于糖尿病病理生理变化正确评估的药物治疗，可有效控制新诊断2型糖尿病患者的糖代谢紊乱。（2）瑞格列奈及格列吡嗪可增加2型糖尿病患者的一相胰岛素分泌及真胰岛素水平。（3）罗格列酮不仅可以增加机体的胰岛素敏感性，减少胰岛素原的分泌，尚可改善一相胰岛素分泌低下者的一相胰岛素分泌功能。（4）新诊断2型糖尿病患者血糖的有效控制，主要与机体胰岛素分泌功能的改善及胰岛素敏感性的增加有关。     

Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets

We investigated the effect of sub-chronic soybean oil (SO) treatment on the insulin secretion and fatty acid composition of islets of Langerhans obtained from Goto-Kakizaki (GK), a model of type 2 diabetes, and normal Wistar rats. We observed that soybean-treated Wistar rats present insulin resistance and defective islet insulin secretion when compared with untreated Wistar rats. The decrease in insulin secretion occurred at all concentrations of glucose and arginine tested. Furthermore we observed that soybean-treated normal islets present a significant decrease in two saturated fatty acids, myristic and heneicosanoic acids, and one monounsaturated eicosenoic acid, and the appearance of the monounsaturated erucic acid. Concerning diabetic animals, we observed that soybean-treated diabetic rats, when compared with untreated GK rats, present an increase in plasma non-fasting free fatty acids, an exacerbation of islet insulin secretion impairment in all conditions tested and a significant decrease in the monounsaturated palmitoleic acid. Altogether our results show that SO treatment results in a decrease of insulin secretion and alterations on fatty acid composition in normal and diabetic islets. Furthermore, the impairment of insulin secretion, islet erucic acid and fasting plasma insulin levels are similar in treated normal and untreated diabetic rats, suggesting that SO could have a deleterious effect on β-cell function and insulin sensitivity.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.