胆囊收缩素对胰腺生理及病理生理的调节作用

胆囊收缩素(ｃｈｏｌｅｃｙｓｔｏｋｉｎｉｎ,ＣＣＫ)是美国学者Ｉｖｙ和Ｏｌｄｂｅｒｇ于1928年从小肠提取物中发现的第三个胃肠激素,具有促进胆囊排空的作用。1945年英国学者发现第四个胃肠激素———促胰酶素(Ｐａｎｃｒｅｏｚｍｉｎ,ＰＺ)。20世纪60年代,瑞典学者ＶｉｋｔｏｒＭｕｔｔ研究认为,胆囊收缩素和促胰酶素系同一多肽激素,故曾命名为ＣＣＫＰＺ[1],目前均称为ＣＣＫ。ＣＣＫ是研究最广泛的胃肠激素之一,它广泛存在于体内许多部位,是在细胞间传递信息的信息肽。除具有经典的循环激素活性外,在哺乳动物,它还是神经递质、生长因子…     

胆囊收缩素对胃蛋白酶原和胃酸分泌的影响

胆囊收缩素(CCK)广泛分布于胃肠道和神经系统,对胃蛋白酶原(PG)和胃酸分泌具有双重影响。体外研究表明CCK由主细胞、壁细胞上相应受体介导促进PG和胃酸的分泌;在体内CCK通过某种途径(如刺激D细胞释放生长抑素)间接抑制PG和胃酸的分泌。CCK对PG和胃酸分泌具有生理性调节作用。十二指肠溃疡患者CCK抑酸机制可能有缺陷。     

胆囊收缩素对胃蛋白酶原和胃酸分泌的影响

胆囊收缩素广泛分布于胃肠道和神经系统，对胃蛋白酶原和胃酸分泌具有双重影响。体外研究表明ＣＣＫ由主细胞、壁细胞上相应受体介导促进ＰＧ和胃酸的分泌；在体内ＣＣＫ通过某种途径间接抑制ＰＧ和胃酸的分泌。     

八肽胆囊收缩素对大肠杆菌致急性肺损伤大鼠的抗炎作用

目的 探讨八肽胆囊收缩素(CCK-8)对大肠杆菌致急性肺损伤(ALI)大鼠肺水肿及炎症反应的抑制作用.方法 将45只雄性SD大鼠按随机数字表法分为3组,ALI/急性呼吸窘迫综合征(ARDS)组、ALI/ARDS+ CCK-8组和对照组.ALI/ARDS组气管注射大肠杆菌制作ALI/ARDS模型;ALI/ARDS+ CC...     

胃泌素/胆囊收缩素受体环对胃癌细胞增殖迁移的影响

目的探索胃泌素/胆囊收缩素受体环对胃癌细胞增殖迁移的影响。方法用免疫细胞化学方法检测人胃癌细胞SGC-7901、AGS和胃黏膜上皮细胞GES-1细胞中胆囊收缩素-B(CCKB)受体的表达。分别培养这3种细胞,用不同终浓度胃泌素(10、100 nmol/L)处理细胞,以未加胃泌素的细胞为对照,用细胞划痕实验和四甲基偶氮唑盐比色法检测细胞的增殖迁移能力。结果胃癌细胞SGC-7901、AGS中CCKB受体表达强阳性,而GES-1细胞中CCKB受体表达弱阳性;不同浓度胃泌素处理细胞后,SGC-7901、AGS细胞的增殖迁移能力明显增强,而GES-1细胞无明显改变;对照组、10 nmol/L胃泌素处理组及100 nmol/L胃泌素处理组中SGC-7901细胞的相对增殖率分别为100%、191.13%、212.65%,AGS细胞的相对增殖率分别为100%、189.27%、209.19%,各组间差异均有统计学意义(P均<0.01);而GES-1细胞的相对增殖率分别为100%、113.01%、116.12%,各组间差异无统计学意义(P均>0.05)。结论 CCKB受体表达水平的高低对胃泌素/CCKB受体环促进胃癌细胞的增殖和迁移起重要作用。     

六种八肽胆囊收缩素（CCK－8）类似物对豚鼠胆囊收缩活性的测定

测定了六种ＣＣＫ－８类似物对豚鼠胆囊肌条的收缩活性，在Ｅ０５０值的基础上与ＣＣＫ－８标准品比较。结果显示，其活性顺序为：类似物（２）＞类似物（１）＝ＣＣＫ一８标准品＝类似物（３）＞类似物（４），类似物（５）及类似物（６）在剂量高达１０－７ｍｏｌ／Ｌ时仍未显示其活性。实验表明：脱去Ｎ－端氨基的ＣＣＫ一８类似物即Ｓｕｃ－ＣＣＫ－７［类似物（２）］较ＣＣＫ一８活性明显增加，有临床价值，在类似物（３）中，甲硫氨酸被正亮氨酸取代，活性可完全保留，类似物（４）因ＧＬＹ２９被Ｄ－ＡＬａ取代，活性显著降低，但仍可表现其激动剂性质，当ＧＬＹ２９被β－ＡＬａ取代时，即类似物（５）失去了收缩胆囊的活性。     

胆囊收缩素对功能性消化不良患者固体胃排空的影响

目前公认胆囊收缩素（ＣＣＫ）对胃运动调节具有生理性意义,我们用核素法观察ＣＣＫ对功能性消化不良（ＦＤ）患者团体胃排空的影响。 一、资料与方法 １．对象：对照组１５例,男１１例,女４例,年龄２３～５８岁,平均年龄２９岁,均无消化系统疾病及胃肠道症状;无腹部手术史。ＦＤ组２８例,男２３例,女５例,年龄２５～５４岁,平均３２岁。诊断标准：（ｌ）消化不良症状至少存在６个月以上,有典型早饱及上腹胀满;（２）经胃镜、Ｘ线、Ｂ超及其他辅助检查排除器质性疾病;（３）排除有胃肠道手术、神经精神疾病、代谢性疾病史。受…     

The effect of serotonin on in vitro insulin secretion and biosynthesis in mice

Summary The effect of serotonin on insulin secretion and biosynthesis was studied using isolated islets of mice. Serotonin produced a small stimulatory effect on insulin secretion when glucose was present in the incubation medium at a low concentration. On the other hand, an inhibition of insulin secretion was obtained with serotonin when glucose in the medium reached 3.0 mg/ml concentration. No significant effect of serotonin was obtained on insulin biosynthesis, neither in the presence of low nor with a high glucose concentration. These results suggest that the effect of this monoamine on insulin secretion is not mediated via its effect on insulin biosynthesis.Supported by Deutsche Forschungsgemeinschaft Bonn-Bad Godesberg, SFB 87 Ulm     

The effect of retinol on Ito cell proliferation in vitro

Hepatic sinusoidal fat-storing Ito cells are felt to represent the primary storage site for hepatic vitamin A and may be important collagen-producing effector cells during hepatic fibrogenesis. The cirrhotic liver generally has a decreased vitamin A content with increased numbers of "transitional" myofibroblasts adjacent to developing fibrous bands. It has been suggested that Ito cells "transform" into these myofibroblasts. The in vivo loss of Ito cell vitamin A can be simulated in vitro as Ito cells spontaneously lose their vitamin A lipid droplets during primary culture. The current study evaluated Ito cell proliferation in vitro with respect to vitamin A content and the extracellular collagen matrix. The cells were grown on a Type I or Type IV collagen matrix to simulate the types of collagens presumed to be present in the space of Disse. Initially it was observed that freshly isolated Ito cells begin to proliferate several days after isolation coincident with the decline of the vitamin A lipid droplets and a decrease in cellular retinyl palmitate. The proliferation rate for passaged Ito cells was similar on either matrix (on Type I collagen: T 1/2 = 2.2 +/- 1.1 days, n = 16; on Type IV collagen: T 1/2 = 3.3 +/- 1.4 days, n = 4; p less than 0.11). This proliferation rate remained constant through Cell Generation 16 and was similar to the rate for primary Ito cells in culture. To evaluate the possibility that primary Ito cell proliferation is causally related to the loss of vitamin A, Ito cells were re-exposed to an increased concentration of retinol in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)     

瘦素对离体大鼠胰岛分泌胰岛素的双向影响

目的 了解不同浓度的瘦素，在不同条件下对离体大鼠胰岛分泌胰岛素的影响。方法 利用细胞培养技术，在不同的葡萄糖浓度（5.6mmol/L或16.7mmol/L）和不同作用时间（10min或2h)下，以0,1,5,10,15,50ak 100μg/L瘦素作用大鼠胰岛，观察其对胰岛素分泌的影响；用放免法检测培养物上清液胰岛素浓度。结果 培养液葡萄糖浓度为5.6mmol/L，培养10min，1μg/L、5μg/L瘦素促进被孵育的胰岛的胰岛素分泌；培养2h,5μg/L瘦素促进基础胰岛素分泌，≥50μg/L瘦素抑制胰岛素分泌。葡萄糖浓度为16.7mmol/L，培养10min，≥50μg/L瘦素抑制胰岛素分泌；培养2h，≥5μg/L瘦素抑制胰岛素分泌。结论 重组瘦素对离体大鼠胰岛分泌胰岛素具有双向作用，并受瘦素浓度、作用时间和环境葡萄糖浓度等因素变化的影响。     

软脂酸对HIT—T15细胞线粒体形态功能和胰岛素分泌的影响

目的观察软脂酸（PA）对HIT-T15细胞凋亡、线粒体结构和功能及胰岛素分泌的影响并探讨可能的机制。方法试验分对照组、0．5 mmol／LPA和1．0 mmol／LPA组,透射电镜观察细胞及线粒体形态,流式细胞仪（FC）和原位末端标记法（TUNEL）检测凋亡率,高效液相色谱法（HPLC）检测细胞ATP／ADP,RT—PCR检测过氧化物酶体增殖物激活受体γ共激活因子1（PGC-1）和核呼吸因子1（NRF-1）mRNA,放免法测基础和葡萄糖刺激后胰岛素分泌（GSIS）。结果PA能使线粒体肿胀、嵴破坏;细胞的凋亡率增加,且FC检测高浓度PA组凋亡率增加更显著;ATP／ADP比率下降;PGC-1mRNA和NRF-1mRNA表达增加,高浓度PA组增加更显著;GSIS下降（P均〈0．05）。结论PA导致HIT-T15细胞的线粒体结构和功能的损害及GSIS下降,可能与PGC-1和NRF-1的调节作用有关。     

The effect of insulin on gastric secretion of potassium

Summary The effect of insulin hypoglycemia on the amount of potassium that could be removed from the stomach of 10 normal dogs was studied. In 5 dogs the gastric secretory volume and the amount of potassium aspirated from the stomach were both increased greatly. In the other 5 dogs, there was no increase in either the volume of secretion or the potassium secreted. A decline in plasma potassium concentration was observed in all 10 animals in response to insulin administration.The author wishes to acknowledge the technical assistance rendered by Thomas Egan, Thomas Kallal, and E. Booker McClaskey.     

Factors controlling insulin secretion in vitro

Summary The development of techniques for maintaining pancreatic isletsin vitro has made it feasible to study the direct effect of various agents and metabolic changes on -cell function. Glucose has to be metabolized within the -cell to provide the signal for insulin secretion, and the importance of the Krebs' cycle is suggested by experimental results. Glucose also stimulates insulin synthesis, but independently from insulin secretion. Growth hormone and placental lactogen enhance both processes, possibly by facilitating the metabolic breakdown of glucose. The role of catecholamines and glucagon in the regulation of insulin secretion has been defined during the past few years.Original material included in this review resulted from work supported by Grant MT-1202, Medical Research Council of Canada, and by funds of the Hospital for Sick Children.     

The effect of oral galactose on GIP and insulin secretion in man

Summary The insulinotropic effect of 50 g galactose given orally to 5 normal volunteers on two occasions — once with and once without a period of hyperglycaemia produced by an intravenous glucose infusion — was studied. Oral galactose caused a rise in plasma GIP from fasting levels of 260±50 ng/l (mean ± S. E. M.) to a maximum of 900±65 ng/l 30 min after ingestion, but in the presence of induced hyperglycaemia the GIP response was significantly diminished and delayed (maximum plasma GIP levels 595+110 ng/l at 45 min, p<0.05). The insulin response to galactose was greatly enhanced by IV glucose (mean area under plasma insulin curve with galactose alone 236.5±66.0, with galactose + IV glucose 451.9+81.6, p<0.025). The mean rise in plasma galactose was significantly lower in the presence of IV glucose (mean peak level 1.97±0.28 mmol/l with galactose alone, 0.69±0.16 mmol/l galactose + IV glucose, p <0.025). Oral galactose caused the release of GIP, which is powerfully insulinotropic in the presence of moderate hyperglycaemia. The lower plasma GIP and galactose levels observed following oral galactose in the presence of IV glucose may be accounted for either by postulating that insulin inhibits the absorption of oral galactose, or that insulin exerts a negative feed-back control on GIP release and accelerates galactose disposition in the body.     

The effect of phenformin on amino acid-induced insulin secretion in diabetics

Twenty-one patients with mild maturity-onset diabetes were given introduodenal infusions of an amino acid mixture (0.5 g amino acids per kg body weight). In 9 other patients L-arginine was infused intravenously in a constant dose of 25 g. Alpha-amino nitrogen, blood glucose and plasma insulin levels were assayed under control conditions and after three days of treatment with phenformin, 150 mg daily, plus the same 150 mg dose 60 min before the second loading. Intraduodenal infusion of the amino acid mixture provoked a greater increase in plasma insulin than intravenous infusion of L-arginine, this increase being significantly inhibited by phenformin only in the first case. Since no evident influence of phenformin on the intestinal absorption of amino acids could be demonstrated, this effect may be explained by a local action on the intestinal wall exposed to high concentrations of the drug, resulting in the inhibition of the insulin secretion stimulating activity of the gut.