葡萄糖依赖性促胰岛素分泌多肽与肥胖

葡萄糖依赖性促胰岛素分泌多肽（GIP）是十二指肠及空肠上段合成、分泌的一种胃肠道激素。GIP被认为是肠促胰岛素轴中主要肠促胰岛素激素，除了调控胰岛素分泌外，GIP具有促进脂肪细胞成熟分化、对营养物质的吸收及脂蛋白酯酶（LPL）的活性等作用。已经证实GIP在肥胖的发生发展中起着重要的作用。近来研究发现抑制GIP信号转导通路能够治疗肥胖，为肥胖的预防和治疗提供了新的靶点。     

GIP/GIPR通路与神经内分泌肿瘤关系的研究进展

葡萄糖依赖性促胰岛素多肽(GIP)是一种可以促进餐后胰岛素分泌的肠促胰岛素。GIP及其受体(GIPR)与神经内分泌肿瘤(NETs)的病理机制及临床表现息息相关。GIP/GIPR通路的异常激活在食物依赖性库欣综合征、糖耐量试验中生长激素(GH)反常升高的肢端肥大症以及胃肠道NETs中最为典型。GIP与肾上腺皮质腺瘤及垂体GH腺瘤异位表达的GIPR结合后, 促进相应激素分泌增加及细胞增殖。再者, 部分生长抑素受体阴性的胃肠道NETs高表达GIPR, 基于GIPR的示踪剂可准确定位此类NETs。深入了解GIP/GIPR在NETs中的病理机制及临床应用可为进一步研究和临床工作提供理论依据。     

肠抑胃肽胰腺外作用的研究进展

肠抑胃肽又称葡萄糖依赖性胰岛素释放多肽（GIP），是一种重要的肠促胰岛素，其受体除分布在胰腺B细胞外，还分布于胃、小肠、脂肪组织、肾上腺皮质、垂体、骨以及脑组织的一些区域等。研究GIP在这些组织及相关疾病，如营养过剩诱导的肥胖症、食物依赖的库欣综合征中的作用可能会为临床上一些常见病和罕见病的治疗带来新的希望。     

葡萄糖依赖性促胰岛素释放肽-受体信号通路与肥胖症的研究进展

葡萄糖依赖性促胰岛素释放肽（GIP）是一种由小肠黏膜上皮K细胞合成并分泌的肠促胰岛素分泌肽,能够刺激胰岛素和胰高糖素的分泌。近年来研究发现,GIP-GIP受体（GIPR）信号通路在肥胖症及其相关代谢异常中起到重要作用。GIP和GIPR基因的多态性与肥胖易感性显著相关。激活GIP-GIPR通路能增加脂肪合成和储存,促进肥...     

胰岛B细胞功能的检测方法及其临床意义

测定B细胞分泌功能对了解糖尿病的发生，发展，预测糖尿病的预后非常必要，其方法主要分为检测葡萄糖刺激，非糖物质刺激的胰岛素分泌以及B细胞分泌其他物质的功能。葡萄糖刺激的方法有高葡萄糖钳夹技术，口服及静脉葡萄糖耐量试验。非糖物质刺激的方法有精氨酸，胰升糖素，甲苯磺丁脲刺激试验。另外，可用于检测的B细胞分泌的其他物质有胰岛素原，C肽，胰淀粉样多肽。在评价B细胞功能的同时需进行胰岛素敏感性参数校正，以获得较高的精确性。     

肠促胰岛素在2型糖尿病中的作用和研究进展

肠促胰岛素(Incretin)具有进食后刺激胰岛素分泌、促进胰岛素生物合成和抑制胰高血糖素分泌等多种生理功能,在维持血糖稳态上发挥了重要的作用.近年来,随着关于肠促胰岛素在2型糖尿病的发病机制和药物治疗方面的研究不断深入,为2型糖尿病的治疗提供了新的思路,开辟了新的途径.     

抵抗素研究进展

抵抗素是由脂肪组织特异分泌的一种多肽类激素，其存在及其单核苷酸多态性可能是联系肥胖与胰岛素抵抗的重要信号分子。抵抗素基因表达的调节可能通过磷脂酰肌醇-3激酶(PI3K)／Akt、丝裂素活化蛋白激酶(MAPK)信号转导通路和CAAT／增强子结合蛋白(EBP)、过氧化物酶体增殖物活化受体(PPAR)转录因子完成。抵抗素通过作用于胰岛素靶器官导致胰岛素刺激的葡萄糖代谢出现异常。除了对胰岛素作用的影响，抵抗素还与脂肪细胞的分化、免疫、炎症、心血管疾病存在联系。     

地黄多糖对肥胖糖尿病大鼠模型的治疗作用及对血清中GLP-1、GIP水平的影响

目的 探究地黄多糖对肥胖糖尿病大鼠的治疗作用,及其对大鼠血清中胰高血糖素样肽-1(GLP-1)、葡萄糖依赖性促胰岛素释放肽(GIP)水平的影响.方法 采用腹腔注射链脲佐菌素(STZ)联合高脂高糖喂养诱导肥胖糖尿病大鼠模型之后,给予不同剂量的地黄多糖,通过检查空腹血糖(FBG)、胰岛素水平、总胆固醇(TC)、甘油三酯(TG)等指标,观察其对大鼠模型的治疗作用,同时采用酶联免疫法测定地黄多糖对各组动物血清中的GLP-1、GIP水平的影响.结果 地黄多糖可以有效改善肥胖糖尿病大鼠的相关生化指标,同时血清中GLP-1、GIP的水平也有所升高.结论 地黄多糖可以通过促进GLP-1、GIP的分泌对肥胖糖尿病大鼠起到治疗作用.     

限食后追赶生长性肥胖与大鼠血浆葡萄糖依赖性胰岛素释放肽水平的关系

目的 探讨限食后追赶生长性肥胖与大鼠血浆葡萄糖依赖性胰岛素释放肽(GIP)水平的相关性.方法 6周龄健康雄性SD大鼠60只按随机数字表法随机分为普通饮食组(n=15,给予普通饮食)、普通饮食追赶生长组(n=15,给予同体重普通饮食组大鼠60%普通饲料限食喂养4周后饲以普通饲料)、高脂饮食组(n=15,给予高脂饮食)和高脂饮食追赶生长组(n=15,给予同体重普通饮食组大鼠60%普通饲料限食喂养4周后饲以高脂饲料),观察大鼠体重及进食量变化.分别于4、6、8周处死部分动物,检测体脂含量及血浆GIP浓度.采用配对t检验和单因素方差分析以及一元线性相关分析进行数据统计.结果 与普通饮食组相比,高脂饮食组、普通饮食追赶生长组和高脂饮食追赶生长组体脂含量[分别为(3.6±0.6)、(7.9±1.5)、(4.6±1.1)、(7.0±1.0)g;t值分别为-2.601、-2.305、-2.501,均P＜0.05]、血浆GIP水平升高[分别为(41±9)、(61±7)、(51±8)、(59±8)pmol/L;t值分别为-6.061、-3.452、-4.651,均P＜0.05].相关分析显示,体脂含量与血浆GIP水平显著相关(r2=0.9407).结论 限食后追赶生长性肥胖与大鼠血浆GIP水平高度相关,可能与追赶生长所引发的病理生理学变化有关.     

糖依赖性胰岛素释放肽在脂肪代谢中的作用

越来越多的研究表明,糖依赖性胰岛素释放肽(GIP)在脂代谢中具有重要的促合成作用,包括对葡萄糖摄取、脂肪酸合成、脂蛋白脂酶活性的刺激,造成脂肪酸在脂肪组织的沉积.同时,GIP可抑制胰高血糖素和异丙肾上腺素诱导的脂肪分解,进而增加脂肪的堆积.在肥胖的动物模型中,长期阻断GIP的信号转导可以明显改善血糖、减轻体重,此外,还可减少高脂饮食诱导的肥胖的发生.以上研究结果为肥胖、糖尿病的预防和治疗提供了一种新的思路.     

肠促胰素的胰腺外作用研究进展

肠促胰素是经食物刺激后由肠道细胞分泌入血、能够刺激胰岛素分泌的一类激素.人体中,胰升糖素样肽1(GLP-1)和糖依赖性胰岛素释放肽((GIP)发挥肠促胰素效应.本文简要介绍肠促胰素的胰腺作用,重点回顾其胰腺外生理作用,以全面评价肠促胰素类药物的临床应用前景.

Abstract：

Incretin is defined as an intestinal hormone released in response to nutrient ingestion, which potentiates the glucose-induced insulin response. In human body, the incretin's effect is mainly induced by two peptide hormones, glucagon-like peptide-I (GLP-I)and glucose-dependent insulinotropic polypeptide (GIP). In order to fully evaluate the clinical advantages of novel agents based on incretin, this review introduces the islet actions of incretin in brief, and mainly focuses on the extra-islet effect of incretin.     

Effects of passage through the digestive tract on incretin secretion: Before and after birth

Aims/IntroductionIt was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia.Materials and MethodsInfants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon‐like peptide‐1 (GLP‐1) and gastric inhibitory peptide/glucose‐dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth.ResultsA total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP‐1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP‐1 (r = 0.47) or GIP (r = 0.49).ConclusionsOur results show that enteral feeding is important for secretion of GLP‐1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP‐1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP‐1 and GIP during the fetal period.     

单纯性肥胖者和糖尿病患者血清胰多肽水平观察

本文用自制胰多肽(PP)放射免疫分析试剂盒,观察了24例单纯性肥胖者和34例糖尿病患者空腹和餐后PP的分泌水平,结果与18例正常人比较,发现肥胖者PP、胰岛素、C肽和血糖均呈高分泌现象;糖尿病病人PP水平也增高,但C肽和胰岛素则降低。     

肠促胰素在2型糖尿病治疗中的作用

肠促胰素是经食物刺激后由肠道细胞分泌入血、具有促进胰岛素分泌作用的一类激素;人体中,胰升糖素样肽1(GLP-1)和糖依赖性胰岛素释放肽(GIP)发挥肠促胰素效应.根据近期发表的研究,本文回顾了肠促胰素的生理作用,同时阐述了 GIP和GLP-1在2型糖尿病治疗中的特点.     

由肠道讲起——从胃肠激素到联合治疗

胰高血糖素样肽(GLP)-1和葡萄糖依赖性促胰岛素释放肽(GIP)等许多胃肠道激素通过影响胰岛素分泌、肝糖代谢和食物摄入调节糖代谢.GLP与GIP的联合、GLP与胰高血糖素的联合提供了治疗糖尿病和肥胖的新途径,而在一个分子中整合3个内源性激素开辟了治疗新理念.     

WNT/β-catenin increases the production of incretins by entero-endocrine cells

Aims/hypothesis  Glucose-dependent insulinotropic peptide (GIP) plays a pivotal role in the regulation of glucose homeostasis. Rates of diet-induced obesity, insulin resistance and type 2 diabetes are decreased when GIP signalling is disturbed in mice, suggesting that GIP plays a role in the onset of type 2 diabetes. WNT signalling is linked to type 2 diabetes and induces synthesis of the other incretin, glucagon-like peptide 1 (GLP-1). GLP-1 analogues improve treatment of type 2 diabetes patients in whom GLP-1 signalling is intact and have captured clinical attention. GIP levels are altered at the onset of type 2 diabetes and later on, while GIP signalling is impaired. Thus, GIP is not a candidate for treatment but might be an important target from a prevention perspective. Hypothesising that hypersecretion of GIP links altered WNT signalling to the onset of type 2 diabetes, we sought to determine whether WNT signalling induces GIP production by entero-endocrine cells. Methods  RT-PCR and chromatin immunoprecipitation (ChIP) were used to study Gip gene induction. Gip promoter elements mediating WNT/lithium induction were identified (electrophoretic mobility shift assay, co-transfection of deletion mutants, ChIP). Results  Lithium or WNT/β-catenin signalling enhanced GIP production by entero-endocrine cells through a conserved site in the proximal Gip promoter. Lithium favours lymphoid enhancer factor-1/β-catenin binding to Gip promoter and diminishes ChIP through T cell factor-4 and histone deacetylase 1. Conclusions/interpretation  Lithium and WNT are incretin inducers in general. This work provides a novel link between WNT signalling, obesity and diabetes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. J. M. García-Martínez and A. Chocarro-Calvo contributed equally to this work.     

Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus

Aims/hypothesis We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes. Materials and methods Ten patients (eight men) with type 2 diabetes (age: 64 [51–80] years; BMI: 23 [21–26] kg/m²; HbA_1c: 6.9 [6.2–8.7]%, values mean [range]) and ten control subjects matched for sex, age and BMI were studied. Blood was sampled on two separate days following a 4-h 50-g OGTT and an isoglycaemic i.v. glucose infusion, respectively. Results Isoglycaemia during the 2 days was obtained in both groups. In the control subjects no difference in glucagon suppression during the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (−36 ± 12 vs −64 ± 23 mmol/l × 45 min; p = NS) was observed, whereas in the group of patients with type 2 diabetes significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (−63 ± 21 vs 10 ± 16 mmol/l × 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion of glucagon-like peptide-1 or glucose-dependent insulinotropic polypeptide between the two groups during OGTT or isoglycaemic i.v. glucose infusion, respectively, could explain this. Conclusions/interpretation Attenuated and delayed glucagon suppression in patients with type 2 diabetes occurs after oral ingestion of glucose, while isoglycaemic i.v. administration of glucose results in normal suppression of glucagon. We suggest that this phenomenon contributes both to the glucose intolerance and to the reduced incretin effect observed in patients with type 2 diabetes.