Ghrelin与糖尿病

1999年Kojima等在小鼠胃内分泌细胞发现一种含28个氨基酸的多肽，为生长激素释放多肽（ghrelin），它能诱导生长激素（growth hormone，GH）的分泌，并与能量代谢、肥胖和胰岛素分泌有关，现将ghrelin与糖尿病的关系综述如下。     

生长素(Gbrelin)对心血管的保护作用

生长素 (ghrelin)是生长激素促分泌素(GHS)受体的内源性配体,它主要合成于胃, 另在十二指肠、小肠、大肠、胰腺、胎盘亦有表达,而在下丘脑弓状核亦检出有其 mRNA 表达.胃体部粘膜下层内分泌细胞中存在 ghrelin 最多,由此分泌入血后, 经血脑屏障作用于下丘脑及垂体而发挥作用,称为肠-脑对话 (bowel-braincross-talk)[1]. Ghrelin 与下丘脑 ghrelin 受体结合后,刺激生长激素 (GH)分泌 [2], 通过胰岛素样生长因子 (GH/ IGF)轴激活合成代谢效应, 调节机体能量代谢, 如维持骨骼肌及心肌生长 [1], 增强食欲, 促进胃肠功能、调节能量平衡, ghrelin 还可能参与调节睡眠-觉醒模式、睾丸功能 [3]抗增殖作用, 目前人们研究发现 ghrelin可以旁 /自分泌的形式,对心血管系统发挥细胞保护作用, 因而吸引越来越多的人进行研究, 成为热门研究课题.     

垂体生长激素腺瘤和胚胎垂体细胞的体外分泌效应

为观察垂体生长激素(GH)腺瘤细胞的体外分泌效应,选择8例垂体GH腺瘤和4例胚胎垂体,采用单层细胞培养技术,在给予生长激素释放激素(GHRH)、生长激素释放肽-2(GHRP-2)后,发现胚胎垂体细胞具有明显的分泌效应,肿瘤细胞(gsp癌基因阳性和阴性)的分泌则表现各异;而生长抑素(SMS)对二类细胞均具有明显的抑制效应.结果表明肿瘤细胞与正常垂体细胞的激素分泌途径存在差异,下丘脑对肿瘤细胞激素分泌不再有调控作用.     

慢性心力衰竭患者服用ghrelin对其左室功能、运动耐量和肌肉萎缩的影响

背景:ghrelin是一种新的生长激素释放肽段,它还可通过非生长激素依赖性机制来诱导血管收缩、抑制交感神经活动以及刺激进食。本试验主要研究ghrelin对慢性心力衰竭(CH F)患者的左室(LV)功能、运动耐量和肌肉萎缩的作用。方法和结果:10例CH F患者通过静脉途径给予人工合成ghrelin(2μm/kg,2次/d),共3周。在给予ghrelin治疗前后,对每例患者进行超声心动图、心肺运动试验以及X线双倍吸收比色法检查,并采集血样。单独给予ghrelin可导致血清GH明显升高(升高25倍)。给药3周则可引起血清去甲肾上腺素水平明显降低(从1132±188ng/L降至655±134…     

生长激素释放多肽通过与生长激素释放因子不同的受体起作用

用固相法合成了生长激素释放因子(GRF),生长激素释放多肤(GHRP)和生长激素释放抑制因子(GRF-AN,D-Arg2-GRF44),并检测了多肽的生物学活性。结果表明1.GRF和GHRP在体内外均可刺激人垂体生长激素(GH)分泌。2.GRF和GHRP体外灌流时均可刺激牛垂体GH分泌。3.GHRP可促进大鼠生长发育。4.GRF-AN可抑制由GRF兴奋的人和动物垂体GH释放,但有较强的选择性,GRF-AN不抑制由GHRP兴奋的GH释放。表明,GRF和GHRP均可兴奋垂体GH分泌,但二者的机制有本质上的区别。     

生长抑素——下丘脑和胃、十二指肠产生的一种激素抑制物

1973年美国Brazeau等从50万头羊的下丘脑中,提取出一种多肽,它可以抑制垂体前叶生长激素的释放,称为生长激素释放抑制激素(Growth hormone release-inhibiting hormone)或生长抑素(Somatostatin)。近年来的研究证明,这种激素不仅可以抑制生长激素的分泌,而且也可以抑制多种其它激素,如促甲     

Ghrelin和BMI对急性胰腺炎患者的预测价值

目的:初步探讨体质指数(BMI)和生长激素释放肽(ghrelin)对于预测急性胰腺炎严重程度的价值。方法:收集确诊的急性胰腺炎患者76例,用酶联免疫吸附实验方法测定急性胰腺炎患者入院和治疗2周后的血清ghrelin、TNF-α和IL-1β水平。结果:本研究中发现重症胰腺炎(SAP)组患者的BMI和入院时ghrelin、TNF-α和IL-1β水平要显著高于轻症急性胰腺炎(MAP)组和对照组,治疗2周后MAP和SAP组的ghrelin、TNF-α和IL-1β水平出现下降。结论:血清ghrelin和BMI可以做为预判急性胰腺炎病情严重程度的指标之一,ghrelin的升高与急性胰腺炎的严重程度有关。     

重组生长激素的研究及临床应用

10 0年前 ,在肢端肥大症病人中首先发现垂体腺肥大 ,从此开创了生长激素 (ＧＨ)的研究时代[1] 。到 195 8年Ｒａｂｅｎ开始应用人体生长激素治疗垂体性侏儒症[2 ] 。在随后的 40年中 ,随着重组ＤＮＡ技术的发展和重组生长激素 (ｒＧＨ)方法的提高 ,ｒＧＨ研究达到了生物化学及分子生物学水平。ｒＧＨ临床应用的安全性及有效性大大地提高 ,目前ｒＧＨ已广泛应用于临床各系统疾病。1　内分泌系统疾病1.1　垂体性侏儒症　应用生长激素治疗垂体性侏儒症已有 40年历史 ,最初应用是从人垂体纯化提取生长激素 ( ｐｈＧＨ ) ,80年代以后发现 ｐｈＧ…     

101例PRL血症的测定

垂体催乳素(PRL)是垂体产生的,由198个氨基酸组成的蛋白激素,它的结构和生物学方面与生长激素(GH)和胎盘催乳素(HPL)属同一类激素,它的产生及分泌受神经内分泌反射的调节,主要由催乳素释放因子(PRF)和催乳素抑制因子(PIF)所完成.垂体催体素激素放免检测是1971年     

脑肠肽Ghrelin的研究进展

1999年首先从大鼠胃黏膜及下丘脑发现的一种新的脑肠肽激素Ghrelin,是迄今发现的唯一生长激素释放激素受体(GHSR)的内源性配体,它能诱导生长激素的释放,调节能量代谢平衡,并在人类各种疾病和病理状态中发挥重要作用。     

Insulin treatment reduces pre-prandial plasma ghrelin concentrations in children with type 1 diabetes.

BACKGROUND: Ghrelin is well recognized as a key factor in regulating appetite and energy homeostasis. The aim of the present study is to characterize the plasma ghrelin concentrations in children with type 1 diabetes at the time of diagnosis and to determine the effect of metabolic control after insulin therapy on circulating ghrelin levels. Also, the relationship between the simultaneous blood glucose concentrations and fasting plasma ghrelin concentrations was explored. MATERIAL/METHODS: This prospective study assessed the changes in pre-prandial plasma ghrelin levels after treatment of type 1 diabetes with insulin. Results: The study comprised 19 children with new onset diabetes mellitus. Mean plasma ghrelin levels declined by 29% in diabetic children post insulin treatment (p=0.007). There was a significant correlation between plasma ghrelin and body mass index (BMI) in children with type 1 diabetes at diagnosis (r=-0.54), but not at follow up. The difference in ghrelin at diagnosis and at 3 month follow up demonstrated an inverse relationship to difference in plasma glucose (r=-0.48). CONCLUSIONS: Plasma ghrelin concentrations could be suppressed in untreated type 1 diabetic children by improved glycemic control following insulin replacement.     

腹膜透析和血液透析患者血浆Ghrelin水平的研究

目的检测腹膜透析和血液透析患者空腹血浆ghrelin水平,探讨影响ghrelin水平的因素及它与炎症、营养等的关系。方法用酶联免疫吸附法(ELISA)测定30名腹膜透析病人、30名血液透析病人和20名健康对照的空腹血浆ghrelin水平并进行比较,同时对透析患者的血浆ghrelin水平与营养指标、炎症指标等进行相关分析。结果透析患者的空腹血浆ghrelin水平明显高于健康对照(P<0.0001),而腹膜透析患者和血液透析患者的血浆ghrelin水平间无统计学差异(P=0.601)。透析患者血浆ghrelin水平与体重指数(BMI)负相关(P=0.004),与血白介素6水平呈正相关(P=0.006),与血前白蛋白水平呈负相关(P=0.037)。另外,营养良好组、轻中度营养不良和重度营养不良组间血浆ghrelin水平差异无显著性(P=0.165),炎症反应明显组和低或无炎症反应组间血浆ghrelin水平差异无显著性(P=0.423)。结论透析患者血浆ghrelin水平明显高于正常人,而腹膜透析和血液透析患者间血浆ghrelin水平差异无显著性。此人群的血浆ghrelin水平与体重指数负相关,而与年龄、其他营养及炎症指标等无明确关系。     

Role of ghrelin in cognitive impairment of hypertensive elders with chronic psychological distress

Objective： To investigate ghrelin level change in combination with psychological stress in the hypertensive old people with cognitive impairment and to explore its effect as well as possible mechanism. Methods： The study population of 300 elders was divided into 2 groups, 148 with hypertension and 152 non-hypertension, who were screened for psychological distress and cognition function, and had blood drawn to measure plasma levels of ghrelin and total cortisol on the same day. Results： The rates of anxiety and cognitive impairment were higher in the hypertension elders, which were negatively correlated with plasma ghrelin level, resulted from chronic cortisol response to anxiety. Conclusion： Chronic plasma cortisol increase to long-term anxiety leads a reduce in ghrelin level which then adversely affects blood pressure and cognitive function in old people. So measuring ghrelin of elders may be a diagnostic tool to predict cognitive development and ghrelin may be a selective antihypertensive medicine for cognitive impairment elders with or without chronic psychological stress     

原发性高血压患者血浆 ghrelin水平的改变及其影响因素

 【目的】研究原发性高血压患者血浆生长激素促分泌素受体(GHSR)的内源性配体 ghrelin水平的改变及抗高血压药物治疗对血浆ghrelin水平的影响。【方法】 入选41 例健康志愿者作为对照组,37 例原发性高血压患者并实施降压治疗,采用酶联免疫法测定健康对照组和原发性高血压患者治疗前后血浆 ghrelin水平及其它内皮相关指标,并分析血浆ghrelin与血压(BP)、体质量指数( BMI)、腰围、腰臀比、血脂、空腹血糖、同型半胱氨酸(Hcy)、内皮素(ET-1)、NO、vWF之间的关系。【结果】 原发性高血压患者血浆ghrelin水平较健康对照组明显升高(P < 0.01),而血浆Hcy、NO水平与对照组比较无明显差异(P > 0.05)。该组经降压治疗9个月后患者BP、BMI、血脂及血浆ghrelin、ET-1、vWF水平均降低(P < 0.01),且血浆Hcy、NO水平无显著变化(P > 0.05)。相关性分析表明血浆ghrelin水平与ET-1呈显著正相关(r = 0.37,P < 0.01),而与血糖、BMI呈负相关(r = -0.29,P < 0.01;r = -0.26,P < 0.05)。多元线性逐步回归分析提示ET-1是影响血浆 ghrelin水平的独立相关因素。【结论】 高血压患者血浆ghrelin水平的显著升高可能与高血压患者血浆中高水平的ET-1刺激了机体自身的ghrelin的代偿分泌有关。     

Serum ghrelin and carotid atherosclerosis in older Japanese people with metabolic syndrome

Ghrelin may play a role in the development of atherosclerosis. However, the effect of serum ghrelin on carotid intima-media thickness (cIMT) (well-established as a surrogate marker to atherosclerosis) in metabolic syndrome (MS), particularly among relatively older subjects, has still not been thoroughly investigated. A total of 101 subjects >60 years of age (mean age, 72.3 years) with MS were enrolled in the study to investigate the relationship between serum total ghrelin and B-mode ultrasonographic cIMT levels. There were significantly positive correlations between cIMT and both age and systolic BP, but cIMT was significantly inversely correlated to ghrelin levels. In the multiple regression analysis for cIMT adjusted by other measured parameters, ghrelin was a significant and independent factor along with age and systolic BP. These findings suggest that decreased ghrelin levels may be related to carotid atherosclerosis among older subjects with MS.     

乙肝后肝硬化患者血清ghrelin、瘦素与胰岛素抵抗的关系

目的:探讨乙肝后肝硬化患者ghrelin、瘦素(Leptin)水平变化规律及其与胰岛素抵抗的关系。方法:选择乙肝后肝硬化患者100例,按肝功能Child A、B、C 3级分组,正常对照组36例,测定各组空腹血糖(FPG)、空腹胰岛素(FINS)、ghrelin及Leptin指标,计算胰岛素抵抗指数(IRS)并进行对比分析。结果:乙肝后肝硬化患者FPG、FINS、IRS、Leptin水平高于对照组,ghrelin水平低于对照组,差异有统计学意义(P<0.01);肝硬化患者A级、B级、C级三组之间FINS、IRS、ghrelin、Leptin差异有统计学意义(P<0.01),FINS、IRS、leptin水平随Child分级升高而升高(P<0.05),ghrelin水平随Child分级的升高而降低(P<0.05)。结论:ghrelin和Leptin水平的变化与乙肝后肝硬化患者的胰岛素抵抗密切相关,ghrelin和瘦素水平的测定对肝硬化病情严重程度的评价有重要临床价值。     

Ghrelin 水平与T2DM 患者认知功能的相关性研究

目的 探讨血清胃饥饿素（Ghrelin）水平与2 型糖尿病（T2DM）患者认知功能的相关性。方法 选取2015 年6 月-2016 年8 月于唐山工人医院内分泌科就诊的T2DM 患者195 例作为研究对象。收集患者的年龄、性别、教育、病程、体重指数、空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯、高密度脂蛋白及低密度脂蛋白等指标,采用酶联免疫法吸附法检测血清Ghrelin 水平。使用简易精神状态量表（MMSE）和重复性成套神经心理状态测验量表（RBANS）对所用患者的认知功能进行评定。依据MMSE评分结果将患者分为认知功能障碍组和非认知功能障碍组,比较以上两组的一般资料及RBANS 量表认知功能评分有无差异。结果 ①与T2DM 非认知功能障碍组相比,认知功能障碍组患者血清Ghrelin 上升（P <0.05）;②经Logistic 回归分析发现,血清Ghrelin 为T2DM 出现认知功能障碍的保护因素（P <0.05）;③血清Ghrelin 与T2DM 患者RBANS 量表即刻记忆、言语功能、注意力、延时记忆及总分呈正相关（P <0.05）。结论 T2DM 伴认知功能障碍患者血清Ghrelin 水平降低,并且与认知功能呈正相关,提示Ghrelin 可能参与了T2DM 患者认知功能障碍的发生及发展过程。     

甲状腺毒症小鼠外周循环中Ghrelin水平的影响因素分析

  目的 探讨甲状腺毒症小鼠循环中Ghrelin水平变化及其影响因素。方法 实验组C57BL6小鼠给予左旋甲状腺激素每日皮下注射,连2周诱发小鼠甲亢,对照组仅注射生理盐水。检测小鼠给药前后体质量、摄食量并采血和留尿。测定空腹血糖、血脂、胰岛素、瘦素水平和甲状腺功能等。实验组小鼠进一步分为自由摄食组、轻度限制摄食组及重度限制摄食组。ELISA方法测定血浆辛酰化和去辛酰化Ghrelin。结果 与对照组比较,自由摄食组甲亢小鼠的非辛酰化Ghrelin水平明显降低,而摄食控制的甲亢小鼠的辛酰化Ghrelin水平明显升高（P<0.05）。实验组血浆辛酰化、非辛酰化Ghrelin水平与血糖水平呈正相关(r值分别为0.417, 0.32, P<0.01),而与个体的终体质量、血清胰岛素、瘦素水平及HOMA-IR指数呈负相关(辛酰化Ghrelin：r值分别为-0.419, -0.511, -0.501, -0.363, P<0.05; 非辛酰化Ghrelin: r值分别为-0.5, -0.609, -0.687, -0.448, P<0.01)。回归分析显示,血糖及瘦素可预测辛酰化Ghrelin水平。结论 甲状腺激素本身可能并非调节Ghrelin分泌的主要因素。甲状腺毒症时Ghrelin水平的变化可能与机体的糖代谢及胰岛素抵抗指数的变化有关。     

Serum ghrelin and leptin levels in adult growth hormone deficiency syndrome

BACKGROUND: In spite of the increasing information that has recently been accumulated on the involvement of ghrelin and leptin in the control of energy balance, the relationship between ghrelin and leptin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in the pathological condition characterized by GH deficiency has been poorly clarified. Therefore, we performed this study to examine the correlation of the plasma levels of ghrelin and leptin with the anthropometric and biochemical markers in GH-deficient (GHD) adults as compared to their healthy cohorts. METHODS: In 60 male adults (GHD; n = 12, healthy control; n = 48, average age: 54 years), we investigated the correlations between the serum leptin and ghrelin levels with the anthropometric and biochemical factors in the control group, as compared to the GHD patients. The diagnosis of GH deficiency was made when peak response for serum GH was <5 microg/L to a GH-provocative test (L-dopa test). All subjects underwent assessment of waist circumference, body mass index (BMI) and percentage body fat for their body composition. Plasma ghrelin, leptin, insulin, GH and IGF-1 were measured. RESULTS: Groups were matched for age, BMI, waist circumference and percent of body fat. Ghrelin and leptin levels were not significantly different between the two groups. There was no correlation between the peak GH level or the GHAUC and the ghrelin concentrations in the GHD subjects. Plasma leptin correlated positively with percentage of body fat, total cholesterol and LDL-cholesterol, but it had no correlation with the peak GH or area under the curve for growth hormone (GHAUC) in the GHD subjects. Plasma ghrelin concentrations were not correlated with the biochemical and anthropometric markers in the subjects with GHD, and ghrelin showed no significant differences in the GHD and control subjects. Leptin concentrations were positively correlated with body fat, but they were not correlated with the levels of either IGF-1 or GH in the GHD patients. CONCLUSIONS: It is possible that ghrelin concentrations appeared normal in the GHD subjects because of the opposing influences of increased adiposity, which reduce ghrelin secretion, and GHD, which may increase it. Further studies are needed to clarify these controversies about the relation of ghrelin and leptin with the GH and IGF-1 levels.     

胃促生长素对脓毒症大鼠脑功能障碍的影响及相关机制

目的探讨炎性因子在脓毒症大鼠脑功能障碍发病机制中的作用及胃促生长素(ghrelin)对脓毒症大鼠脑功能和脑部炎性反应的影响。方法将64只雄性Sprague-Dawley(SD)大鼠随机分为假手术组(Sham组)、假手术+ghrelin组(Sham+ghrelin组)、盲肠结扎穿孔(CLP)组及CLP+ghrelin组,每组16只。采用CLP法制作大鼠脓毒症脑病模型。Sham+ghrelin组和CLP+ghrelin组于造模后即刻及12h后腹腔注射ghrelin80μg/kg,Sham组及CLP组于相应时间点腹腔注射等量的0.9%氯化钠溶液。将每组再分为3个亚组:第1亚组6只,于术后6h采用动物神经功能评分表对大鼠进行评分,而后麻醉断头取左侧海马组织,采用酶联免疫吸附试验检测肿瘤坏死因子(TNF)-α及白细胞介素(IL)-6的表达情况;第2亚组6只,于术后24h进行上述处理;第3亚组4只,于术后24h灌注取脑组织行尼氏染色后进行病理学检查。结果造模后24h,CLP组及CLP+ghrelin组大鼠的神经功能评分均显著低于Sham组及Sham+ghrelin组(P值均<0.05),CLP+ghrelin组显著高于CLP组(P<0.05),Sham+ghrelin组与Sham组间的差异无统计学意义(P>0.05)。造模后6、24h,Sham组与Sham+ghrelin组间海马组织中TNF-α及IL-6表达的差异均无统计学意义(P值均>0.05),CLP组及CLP+ghrelin组海马组织中TNF-α及IL-6的表达水平均显著高于Sham组及Sham+ghrelin组(P值均<0.05),CLP+ghrelin组显著低于CLP组(P值均<0.05)。CLP组大鼠海马神经元明显变性、坏死、丢失,排列疏松,部分神经元核固缩,细胞质内尼氏小体减少;CLP+ghrelin组与CLP组相比,上述病理改变明显减轻,但未完全消失。结论 ghrelin对脓毒症大鼠的脑功能起到一定的保护作用,其机制可能与下调炎性因子TNF-α及IL-6的表达而减轻海马神经元的损伤有关。