Effects of glucagon, secretin, and vasoactive intestinal polypeptide on gastric somatostatin and gastrin release from isolated perfused rat stomach

To investigate the role of gastric somatostatin on gastrin secretion, glucagon, secretin, and vasoactive intestinal polypeptide (VIP) were perfused in the isolated pancreas-spleen-duodenum deprived preparation of rat stomach. After a preperfusion with 4.6% dextran Krebs-Ringer bicarbonate buffer containing 5.5 mM glucose, glucagon, secretin, and VIP at the concentrations of 10(-8), 10(-7), and 10(-6) M were infused into the left gastric artery at a constant flow of 2 ml/min for 15 min. All glucagon, secretin, and VIP evoked dose-dependent increases of somatostatin secretion with a simultaneous dose-related decrease of gastrin release. Furthermore, a significant correlation was found between the increase of somatostatin release and the decrease of gastrin secretion induced by glucagon, secretin, and VIP. These results raise the possibility that the suppression of gastrin secretion induced by glucagon, secretin, and VIP may, at least in part, be mediated by local action of gastric somatostatin.     

The effect of vasoactive intestinal peptide, secretin, and glucagon on human duodenal bicarbonate secretion

Duodenal luminal acidification increases duodenal mucosal bicarbonate production and also releases both secretin and vasoactive intestinal peptide (VIP). The effect of these two structurally similar peptides on human duodenal bicarbonate production has not been examined in humans. Our purpose was therefore to assess the effect of VIP and secretin and also glucagon, a homologous hormone, on human duodenal bicarbonate secretion. A 4-cm portion of either proximal or distal duodenum was isolated and perfused with iso-osmolar NaCl. Pure porcine VIP (200 and 400 pmol/kg-h intravenously) significantly increased proximal duodenal bicarbonate secretion. Although secretin (0.01 to 0.18 CU/kg-h intravenously) markedly increased pancreatic bicarbonate secretion, it failed to alter duodenal mucosal bicarbonate output in either the proximal or the distal duodenum. Glucagon (1 to 8 micrograms/kg-h intravenously) did not affect proximal duodenal mucosal bicarbonate output. It is concluded that VIP, but neither secretin nor glucagon, significantly stimulates human duodenal mucosal bicarbonate secretion.     

生长激素对脑出血大鼠血清白蛋白含量和小肠黏膜形态学的影响

目的 评价重组人生长激素(recombinant human growth hormom,rhGH)对脑出血大鼠血清白蛋白水平和小肠黏膜形态学的影响.方法 采用自体血注射法制作大鼠脑出血模型.56只SD大鼠分为假手术组(n=8),rhGH组(n=24;腹腔注射rhGH,1 U/kg,1次/d)和生理盐水对照组(n=24;腹腔注射等量生理盐水,1次/d),后两组均分别再分为术后1、7和14 d组(每组n=8).检测各组大鼠不同时问点血清白蛋白浓度,HE染色和图像分析观察小肠黏膜形态学改变.结果 脑出血各时间点,生理盐水对照组血清白蛋白水平均较假手术组显著降低(P均<0.01);rhGH组血清白蛋白水平随治疗进程逐渐增高,但仅在14 d时显著高于生理盐水对照组[(39.93±1.98)g,L对(37.93±1.57)g,L,P<0.01].脑出血后1 d和7 d时,rhGH组小肠绒毛高度和黏膜厚度与生理盐水对照组无显著差异,但14 d时显著增高(P<0.01).脑出血后1、7和14 d小肠绒毛面积进行性缩小,且rhGH组较生理盐水对照组随治疗进程进行性增高(P<0.01).脑出血后1 d和7 d.rhGH组肠腺深度较生理盐水对照组增高(P<0.01),但14 d时无显著差异;脑出血1 d,rhGH组组肠腺密度较生理盐水对照组显著增高(P<0.01),7 d时增高不显著,14 d时不仅不增反而稍有降低.结论 脑出血大鼠血清白蛋白水平较假手术组显著下降;脑出血可引起小肠黏膜损害.rhGH可提高脑出血大鼠血清白蛋白水平,不论在脑出血早期还是后期均可不同程度减轻小肠黏膜损伤,后期改善更为显著.rhGH对小肠黏膜损伤的改善程度与血清白蛋白水平的升高程度呈正相关.     

肠内生态营养对创伤后大鼠肠屏障功能的影响

目的:研究肠内生态营养对创伤后大鼠肠道屏障功能的影响.方法:将30只Wistar大鼠随机分为3组,即对照组、普通肠内营养组和肠内生态营养组.胃造瘘术后分别给予普通饲料、肠内营养剂和肠内生态营养剂7 d,检测小肠黏膜形态学参数和黏膜IgA ,CD3 ,CD4 和CD8 细胞数量.结果:肠内生态营养组的小肠绒毛高度(205.4 μmvs 177.7 μm,P＜0.05)、肠腺隐窝深度(99.4 μmvs 77.7 μm,P＜0.05)、黏膜厚度(299.9μm vs 267.0 μm,P＜0.05)以及绒毛表面积(10 321.5μm2 vs 8927.6 μm2,P＜0.05)均高于对照组,肠内生态营养组和普通肠内营养组比较差异无显著性(P＞0.05).肠内生态营养组大鼠小肠黏膜中IgA 细胞(21.2 vs 17.5,19.4,P＜0.05)和CD3 (24.2 vs 20.2,22.1,P＜0.05),CD4 (13.4vs 8.9,11.0,P＜0.05)、CD8 (18.7 vs 12.6,15.4,P＜0.05)细胞数均高于对照组和普通肠内营养组.结论:肠内生态营养能较好的改善创伤后大鼠的小肠机械屏障功能,促进小肠黏膜屏障功能的恢复,增强其肠道免疫功能.     

Effect of secretin, pancreozymin OP-CCK, and glucagon on bile flow and bile lipid secretion in rats.

Rats equipped with biliary, duodenal, and vena cava cannulae and supplemented with Na taurocholate received 4 hour infusions of gastrointestinal hormones. Boots secretin increased bile flow by 63% and bile acid, cholesterol, and phospholipid output by 75, 96, and 73% respectively. This stimulatory effect on bile flow and bile acid secretion was observed also in the four hour postinfusion period. Kabi secretin had practically no effect on bile secretion. Boots pancreozymin stimulated bile flow by 45% and to some extent also stimulated bile acid output. OP-CCK and glucagon stimulated mainly bile flow rate.     

Comparative effects of synthetic and natural secretin on pancreatic secretion and on secretin,insulin, and glucagon levels in man

The effect of synthetic secretin (Roche) on exocrine pancreatic secretion and on secretin, insulin, and glucagon levels was determined and compared with that of pure natural porcine secretin (GIH, Karolinska Institutet, Stockholm) in 10 healthy volunteers. The two secretin preparations were found to be equipotent. Equipotency applies to pancreatic secretion and to secretin and insulin plasma levels, whereas the plasma levels of glucagon were not affected by either drug. It is concluded that this synthetic secretin preparation is suitable for clinical and research purposes.     

The effects of glutamine on intestinal epithelial cell proliferation in parenterally fed rats

BACKGROUND: Several papers have indicated that glutamine is a preferred fuel for the enterocyte and that it can increase intestinal epithelial cell proliferation. AIMS: To investigate the effects of glutamine on intestinal epithelial cell proliferation in the parenterally fed rat. METHODS: Five groups of six rats were fed parenterally; a group of orally fed rats was also studied. Crypt cell proliferation was studied after six days using native mitoses in microdissected crypts and bromodeoxyuridine labelling. RESULTS: No effect of treatment was seen on intestinal weight; however, the weights of the small intestine, caecum, and colon were all significantly heavier in the orally fed group than in the total parenteral nutrition groups (p<0.001). There was no effect of any of the glutamine treatments on mitotic activity in the small intestine. In the colon there was a small increase in native mitoses with glutamine (p=0.03). There was also an indication of increased proliferative activity in the first fifth of the small intestine and colon with glutamine. Little effect of glutamine on bromodeoxyuridine labelling in either site was observed, but there was a small but significant reduction in growth fraction of the colon of the glutamine treated group. The labelling distribution curve from sections and the mitotic distribution curve obtained from crypt squashes showed a good correlation. CONCLUSION: Glutamine has a small, but significant effect on mitotic activity but only in the colon. Modest effects on the distribution of labelled cells were also seen.     

Hyperenteroglucagonaemia and small intestinal mucosal growth after colonic perfusion of glucose in rats.

Beside intraluminal factors, humoral agents play an important role in intestinal adaptation. Enteroglucagon, the mucosal concentration of which is maximal in the terminal ileum and colon, is the strongest candidate for the role of small intestinal mucosal growth factor. The present experiment was designed to study the role of colonic enteroglucagon in stimulating mucosal growth in rats with a normal small intestine. After eight days of glucose large bowel perfusion, enteroglucagon plasma concentrations were 120.7 +/- SEM 9.2 pmol/l, versus 60.1 +/- 6.8 in mannitol perfused control rats (p less than 0.001). Gastrin, cholecystokinin, neurotensin, pancreatic glucagon, and insulin plasma concentrations were unchanged. Crypt cell proliferation, measured by the vincristine metaphase arrest technique, increased significantly in the small intestine of glucose perfused animals (p less than 0.005-0.001) in comparison with the controls. This resulted in a greater mucosal mass in both proximal and distal small bowel: mucosal wet weight, DNA, protein and alpha D-glucosidase per unit length intestine were all significantly higher (p less than 0.05-0.001) than in mannitol perfused rats. Our data, therefore, support the hypothesis that enteroglucagon is an enterotrophic factor and stress the possible role of the colon in the regulation of small bowel trophicity.     

Additive interaction of pentagastrin and secretin on pancreatic growth in rats

The role of gastrin in regulating pancreatic growth and its interaction with secretin is unclear. We determined the dose-response relationships of pentagastrin for gastric and pancreatic secretion. Doses that stimulated gastric and pancreatic secretion were given every 8 h for 3 or 5 days; trophic responses of pancreas, oxyntic gland area, duodenum, and colon were compared. Interaction of secretin and pentagastrin on pancreatic growth was measured after 5 days of treatment. Pentagastrin was 250 times less potent for stimulation of pancreatic versus gastric secretion. A submaximal dose of pentagastrin for stimulating pancreatic enzyme secretion doubled pancreatic deoxyribonucleic acid synthesis after 3 days. Pentagastrin caused dose-related increases in pancreatic weight after 3 and 5 days. Pentagastrin had no effect on weight, deoxyribonucleic acid synthesis, or deoxyribonucleic acid content of oxyntic gland area, duodenum, or colon. Secretin had additive effects on pentagastrin-induced pancreatic growth. The pancreas appears to be more sensitive than other organs to trophic effects of pentagastrin. Secretin has additive rather than inhibitory effects on pentagastrin-induced pancreatic growth.     

Effects of intestinal mucosal blood flow and motility on intestinal mucosa

AIM:To investigate the role of intestinal mucosal blood flow(IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury.METHODS:Sixty-four healthy male Wistar rats were divided randomly into two groups:traumatic brain injury(TBI) group(n = 32),rats with traumatic brain injury;and control group(n = 32),rats with sham-operation.Each group was divided into four subgroups(n = 8) as 6,12,24 and 48 h after operation.Intestinal motility was measured by the propulsion ratio o...     

Effects of colchicine on intestinal mucosal dehydrogenases

Summary Histochemical methods have shown that colchicine has an apparent rapid inhibitory effect on LDH, SDH, GL-6-PDH, NADH dehydrogenase, and NADPH dehydrogenase in the mucosa of the small intestine of mice. This colchicine effect is qualitatively similar regardless of the dose of the drug given, although a single large dose (1.5 mg./kg.) did produce arrest of the mitosis in metaphase, while a single small dose (0.24 mg./kg.) did not produce abnormal histologic changes in any of the tissues examined.The importance of this effect of colchicine is discussed and related to the inhibition of other enzyme systems, functional activities and turn-over rate of intestinal mucosa, and the fate of colchicine in the body. In contrast to observations of the effect of irradiation on dehydrogenases, colchicine decreases dehydrogenase activity almost instantly.Since the site of primary action of colchicine is not known, a single explanation for the antimitotic effect of large doses and the therapeutic effect of small doses given to patients with gout is still elusive.Supported by grants CA-04980 and 2A-5286 from the U. S. Public Health Service.Trainee under Gastroenterology Training Grant TI AM 5286 from the U. S. Public Health Service. Service;     

Effects of electroacupuncture on inflammatory response and intestinal mucosal barrier in obese rats with insulin resistance

正Objective To observe the effects of electroacupuncture (EA) on inflammatory response and intestinal mucosal barrier in obese rats with insulin resistance,and to explore the mechanism of EA on improving insulin resistance in rats.Methods Among 45 Wistar male rats,15rats were randomly selected and fed with common diet.After eight weeks,10 rats were randomly selected and divided into the normal group.The remaining 30 rats were fed with high-fat diet for 8 weeks to establish obesity mod-     

复合膳食纤维对实验性溃疡性结肠炎大鼠肠黏膜屏障功能的影响

目的 观察添加复合膳食纤维(DFC)的肠内营养(EN)对实验性结肠炎大鼠肠黏膜屏障功能的影响.方法 将96只SD大鼠用乙酸灌肠法制成结肠炎模型后随机分成3组,C组给予不含DFC的整蛋白型肠内营养粉剂(商品名:能全素);T1组和T2组分别给予含整蛋白型肠内营养 粉剂和DFC的EN.DFC由可溶性膳食纤维(SDF)和不溶性膳食纤维(IDF)按一定比例配制,T1组和T2组中,SDF和IDF的比例分别为1:2和1:3.检测EN后第1、3、5、7天大鼠血浆D-乳酸浓度和血浆二胺氧化酶(DAO)活性并取肠道标本观察肠黏膜变化情况.结果 第3、5、7天的T1组与T2 组血浆D-乳酸浓度和DAO活性较C组下降(P<0.05),T1组与T2组间差异无统计学意义(P>0.05).各时间点T1组与T2组结肠损伤组织学评分均较C组下降(P<0.05),第5、7天T2组较T1组评分下降幅度大(P<0.05).结论 结肠炎大鼠用含有DFC的EN可降低肠道通透性,对肠黏膜屏障有一定的保护作用,不同比例的SDF和IDF 对肠黏膜保护效果不同,适量增加IDF的比例可以增加这种保护效果.     

Interaction of secretin and glucagon on exocrine pancreatic secretion.

Inhibition of secretin-stimulated pancreatic secretion by glucagon was studied in anesthetized dogs. Two external pancreatic fistulas were prepared in dogs for both simultaneous and separate collection of pancreatic juice secreted by the right and left lobes. Two series of experiments were preformed. In the first, graded doses of glucagon (2.5 to 20 micrograms/kg/hr) were administered against a background infusion of 2 CHR U/kg/hr of secretin. In the second, a constant dose of glucagon (20 micrograms/kg/hr) was given against a background infusion of secretin doubling from 1 to 8 U/kg/hr. Infusion of glucagon was started when flow rate became nearly constant, and continued for 60 minutes in each dose. Glucagon produced the dose-related reduction in flow rate and bicarbonate secretion, but not in amylase secretion. This inhibitory effect was almost the same in size between the right and left lobes. No significant change of plasma secretin was observed during glucagon infusion. Michealis-Menten analysis of the dose in slopes (Km) and similar intercepts of Y-axis (CMR). These results suggest that glucagon inhibits competitively secretin-stimulated pancreatic secretion by acting probably on the same receptor as secretin.     

Effect of secretin on growth of stomach,small intestine,and pancreas of developing rats

Secretin is present in the intestine of a number of developing species, and plasma secretin levels are elevated in newborn pigs and humans. Secretin stimulates the growth and affects the enzymatic composition of the stomach, small intestine, and pancreas in adult rats. This suggests a possible role for secretin in the rapid postnatal growth of these organs. We investigated this hypothesis by injecting rats subcutaneously with secretin (100 g/kg) every 12 hr for seven days beginning on postnatal day 3, 6, 13, or 24. Growth parameters (weight, content of protein, DNA) as well as the composition of organ-specific enzymes of the stomach, small intestine, and pancreas were measured. Secretin increased growth parameters of the stomach and small intestine in a similar pattern, and in a quantitatively different fashion from that observed in the pancreas. Secretin's effects were also dependent on postnatal age for all organs studied. These data demonstrate that secretin can influence organ growth and enzyme composition of the stomach, small intestine, and pancreas of developing rats and may be one factor regulating growth and development of these organs.This work was supported by funds from the Medical Research Service of the Veterans Administration.     

Effect of theophylline on glucagon and secretin stimulated bile flow

This experiment was performed to determine the effect of theophylline on glucagon and secretin stimulated bile flow. We intended to determine the effect of theophylline, a proposed stimulant of canalicular bile flow, on the bile flow response produced by well-recognized stimulants of canalicular (glucagon) and ductular (secretin) bile flow. Dogs with chronic bile fistulas were used. Dose-response curves for glucagon and secretin were produced by administration of a wide range of glucagon and secretin doses. The effect of 20 mg/kg/hr theophylline on the dose-response curves was determined. Theophylline significantly increased the bile flow and bile electrolyte changes produced by glucagon at low doses but not at maximal doses of glucagon for stimulation of bile flow. Theophylline significantly increased bile volume and bile electrolyte changes at all doses of secretin, including maximal doses. These results suggest that theophylline and glucagon, both purported to be stimulants of canalicular bile flow in dogs, utilize the same receptor mechanism to stimulate bile flow. The effects of secretin, a proposed ductular stimulant, are potentiated by theophylline. On a functional basis, it is possible that there are separate canalicular and ductular loci of hormone action in stimulation of bile secretion.