RESUMO
OBJECTIVES: Dietary fibers, such as fructooligosaccharide (FOS) and partially hydrolyzed guar gum (PHGG) have several gastrointestinal functions. The aims of this study were to evaluate the effect of acute ingestion of FOS and PHGG on the percentage of gastric emptying and small intestinal transit and to evaluate the effect of these dietary fibers on the levels of intestinal hormones-active glucagon-like peptide-1, pancreatic polypeptide, and gastric inhibitory peptide-and their effect on feelings of hunger and satiety and the desire to eat. METHODS: In this crossover, randomized controlled clinical trial, we compared the effects of these two fibers on gastrointestinal transit. The tests were performed using scintigraphy. On three different days, healthy participants consumed a test meal containing 20 g of digestible maltodextrin (placebo), 20 g of FOS, or 20 g of PHGG. RESULTS: The gastric emptying of the FOS-based diet (84.2 ± 9.4%) within 2 h was statistically increased compared with the placebo and PHGG-based diets (78 ± 10.2% and 74 ± 15.3%, respectively; P < 0.05). However, a reduction in small intestinal transit was observed after consumption of both FOS- and PHGG-based diets (28.5 ± 15.56% and 24.2 ± 13.7%, respectively) compared with the placebo diet (41.20 ± 15.4%; P < 0.05). There were no changes in the levels of intestinal hormones, feeling of hunger and satiety, or desire to eat after consuming the three diets (P > 0.05). CONCLUSION: The acute intake of FOS increased gastric emptying, whereas both FOS and PHGG reduced small intestine transit without altering the levels of intestinal hormones, hunger feelings and satiety, or the desire to eat.
Assuntos
Hormônios Gastrointestinais , Trânsito Gastrointestinal , Fibras na Dieta/farmacologia , Galactanos , Hormônios Gastrointestinais/farmacologia , Humanos , Mananas/farmacologia , Oligossacarídeos , Gomas VegetaisRESUMO
The guanylin family of peptides has 3 subclasses of peptides containing either 3 intramolecular disulfide bonds found in bacterial heat-stable enterotoxins (ST), or 2 disulfides observed in guanylin and uroguanylin, or a single disulfide exemplified by lymphoguanylin. These peptides bind to and activate cell-surface receptors that have intrinsic guanylate cyclase (GC) activity. These hormones are synthesized in the intestine and released both luminally and into the circulation, and are also produced within the kidney. Stimulation of renal target cells by guanylin peptides in vivo or ex vivo elicits a long-lived diuresis, natriuresis, and kaliuresis by both cGMP-dependent and independent mechanisms. Uroguanylin may act as a hormone in a novel endocrine axis linking the digestive system and kidney as well as a paracrine system intrarenally to increase sodium excretion in the postprandial period. This highly integrated and redundant mechanism allows the organism to maintain sodium balance by eliminating excess sodium in the urine. In addition, small concentrations of the atrial natriuretic peptide (ANP) can synergize with low concentrations of both guanylin or uroguanylin, which do not induce natriuresis per se, to promote significant natriuresis. Interestingly, the activation of the particulate guanylate cyclase receptors by natriuretic peptides can promote relaxation of animal and human penile erectile tissue and increase intracavernosal pressure to induce penile erection. These peptides can be prototypes for new drugs to treat erectile dysfunction, especially in patients with endothelial and nitrergic dysfunction, such as in diabetes.
Assuntos
Fator Natriurético Atrial/metabolismo , Hormônios Gastrointestinais/metabolismo , Hormônios Gastrointestinais/farmacologia , Guanilato Ciclase/metabolismo , Peptídeos Natriuréticos/metabolismo , Peptídeos Natriuréticos/farmacologia , Animais , HumanosRESUMO
Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 microM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 microM; guanylin - 0.2 microM) it promoted increases in urine flow (DeltaUF of 0.25 +/- 0.09 mL.g(-1)/min, P < 0.05) and Na+ excretion (% Delta ENa+ of 18.20 +/- 2.17, P < 0.05). BTCI (1.0 microM) also increased %ENa+ (from 22.8 +/- 1.30 to 34.4 +/- 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 microM) induced increases in glomerular filtration rate (GFR; from 0.96 +/- 0.02 to 1.28 0.02 mL.g(-1)/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.
Assuntos
Hormônios Gastrointestinais/farmacologia , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Natriurese/efeitos dos fármacos , Peptídeos Natriuréticos/farmacologia , Inibidores de Proteases/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Glomérulos Renais/fisiologia , Túbulos Renais/fisiologia , Masculino , Natriurese/fisiologia , Proteínas de Plantas/farmacologia , Ratos , Ratos Endogâmicos WKYRESUMO
Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 µM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 µM; guanylin - 0.2 µM) it promoted increases in urine flow (deltaUF of 0.25 ± 0.09 mL.g-1/min, P < 0.05) and Na+ excretion ( percent delta ENa+ of 18.20 ± 2.17, P < 0.05). BTCI (1.0 µM) also increased percentENa+ (from 22.8 ± 1.30 to 34.4 ± 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 µM) induced increases in glomerular filtration rate (GFR; from 0.96 ± 0.02 to 1.28 0.02 mL.g-1/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.
Guanilina e uroguanilina são peptídeos pequenos, ricos em cisteína, envolvidos na regulação da homeostase de fluidos e eletrólitos através da ligação e ativação da guanilato ciclase expressa no intestino e nos rins. A guanilina é menos potente do que a uroguanilina como agente natriurético e é degradada in vitro pela quimiotripsina devido a características estruturais únicas no domínio bioativo do peptídeo. Portanto o objetivo deste trabalho foi verificar se a guanilina é degradada por proteases tipo quimiotripsina, presentes na membrana da borda em escova dos rins. Para esta investigação, foi usado o modelo do rim isolado de rato perfundido. A Guanilina (0,2 µM) não induziu mudanças na função renal. Entretanto, quando pré-tratada com inibidor de tripsina e de quimiotripsina de black-eyed pea (BTCI - 1,0 µM; guanilina - 0,2 µM) promoveu um aumento no fluxo urinário (deltaUF de 0,25 ± 0,09 mL.g-1/min, P < 0,05) e na excreção de Na+ ( por centoDENa+ de 18,20 ± 2,17, P < 0,05). BTCI (1,0 µM) também aumenta por centoENa+ (de 22,8 ± 1,30 a 34,4 ± 3,48, P < 0,0590 minutos). Além disto, BTCI (3,0 µM) induziu um aumento da taxa de filtração glomerular (GFR; de 0,96 ± 0,02 para 1,28 ± 0,02 mL.g-1/min, P < 0,05, 60 minutos). O presente trabalho sugere fortemente que proteases semelhantes à quimiotripsina desempenham um papel no metabolismo renal de guanilinas e descreve, pela primeira vez, os efeitos renais induzidos por um membro da família de inibidores de proteases do tipo Bowman-Birk.
Assuntos
Animais , Feminino , Masculino , Ratos , Hormônios Gastrointestinais/farmacologia , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Natriurese/efeitos dos fármacos , Peptídeos Natriuréticos/farmacologia , Inibidores de Proteases/farmacologia , Relação Dose-Resposta a Droga , Glomérulos Renais/fisiologia , Túbulos Renais/fisiologia , Natriurese/fisiologia , Proteínas de Plantas/farmacologia , Ratos Endogâmicos WKYRESUMO
Guanylin and uroguanylin are two novel peptides that activate membrane-bound guanylate cyclases found in the kidney and intestine, influencing fluid and electrolyte homeostasis by cyclic GMP. Their natriuretic and kaliuretic activities are well documented. Since guanylin is inactivated by chymotrypsin in vitro, experiments were designed to evaluate the role of chymotrypsin-like proteases in renal metabolism of guanylin. Using the isolated perfused rat kidney, guanylin and a recombinant derivative containing a lysine residue in the N-terminus of the native peptide was tested. There were three experimental groups. In the first group, lys-guanylin (0.1-2.5 microg/ml) was placed into perfusate reservoir. In the second group, chymostatin (6 microg/ml), a chymotrypsin inhibitor, was placed into solution. In the third group, after 30 min. of perfusion with chymostatin (6 microg/ml), guanylin (0.3 microg/ml) was placed into solution. A maximal decrease in fractional Na+ reabsorption (%TNa+) was achieved at 1.0 microg/ml of lys-guanylin (from 73.25+/-2.29 to 54.97+/-0.10, P<0.05). Lys-guanylin (1.0 microg/ml) also decreased fractional K+ reabsorption (%TK+) from 59.26+/-3.93 to 30.75+/-0.78 (P<0.05). Chymostatin had no detectable effects in electrolyte reabsorption in this assay. When introduced after chymostatin, guanylin lowered %TNa+ (from 81.2+/-1.86 to 72.6+/-2.45, P<0.05) and %TK+ (from 69.4+/-4.12 to 65.8+/-2.81, P<0.05). At this subthreshold concentration, guanylin alone lacks effects in %TNa+ or %TK+. Furthermore, the ability of both peptides to promote increases in intestinal fluid secretion was evaluated in the in vivo suckling mouse model. When administered per os, guanylin failed to stimulate intestinal secretion. When chymostatin was present in the test solution, guanylin induced intestinal secretion in this assay. In marked contrast, lys-guanylin alone induced diarrhoea in the suckling mouse. The present paper concludes that guanylin undergoes metabolism in target tissues such as the intestine and kidney and its lysine-containing analogue retains full biological activity.
Assuntos
Diuréticos/farmacologia , Hormônios Gastrointestinais/farmacologia , Rim/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Animais Lactentes , Diuréticos/síntese química , Diuréticos/farmacocinética , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hormônios Gastrointestinais/síntese química , Hormônios Gastrointestinais/farmacocinética , Técnicas In Vitro , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Dados de Sequência Molecular , Peptídeos Natriuréticos , Oligopeptídeos/farmacologia , Peptídeos/síntese química , Peptídeos/farmacocinética , Perfusão , Ratos , Ratos Endogâmicos WKY , Fatores de TempoRESUMO
Las hormonas gastrointestinales son químicamente aminas y polipéptidos, que de acuerdo a la secuencia de sus aminoácidos se agrupan en familias. Son producidas por una gran variedad de células distribuidas en todo el intestino y páncreas, así como en algunas porciones del sistema nervioso central. Se describen las principales acciones fisiológicas conocidas hasta ahora y las aplicaciones diagnósticas y usos terapéuticos de algunas de ellas
Assuntos
Hormônios Gastrointestinais/fisiologia , Histocitoquímica , Hormônios Gastrointestinais/farmacologia , Hormônios Gastrointestinais/uso terapêutico , MéxicoRESUMO
A atividade mioelétrica do esfíncter de Oddi foi avaliada tanto nos estados de jejum, como prandial e após a administraçäo de hormônios gastrointestinais que podem desempenhar uma importante funçäo no controle da motricidade do esfíncter de Oddi. A eletromiografia do esfíncter de Oddi e do trato gastrointestinal foi realizada em 21 opossums em jejum e após a administraçäo de 20 Cal/kg de lipídios, proteínas, carboidratos ou de uma mistura isocalórica desses três alimentos. O efeito de hormônios gastrointestinais (colecistoquinina, gastrina, glucagon e secretina) também foi estudado. O segmento proximal do esfíncter de Oddi gerou potenciais de açäo espontâneos que se propagaram para o segmento distal do esfíncter. O esfíncter de Oddi apresenta uma variaçäo na freqüência dos potenciais de açäo durante o jejum que se correlaciona com a atividade mioelétrica do trato gastrointestinal, denominada complexo mioelétrico migratório. Após a administraçäo de alimentos, o complexo mioelétrico migratório foi abolido e substituído por um outro de atividade mioelétrica prandial, cuja duraçäo e freqüência dos potenciais de açäo dependiam do tipo de alimento. A colecistoquinina e a pentagastrina aumentaram e o glucagon e a secretina diminuiram a freqüência dos potenciais de açäo no esfíncter de Oddi. Conclui-se que o esfíncter de Oddi pode desempenhar a funçäo importante de propelir e coordenar o tempo e o volume de drenagem para o duodeno
Assuntos
Animais , Eletromiografia , Hormônios Gastrointestinais/farmacologia , Esfíncter da Ampola Hepatopancreática/fisiologia , Colecistocinina/farmacologia , Glucagon/farmacologia , Pentagastrina/farmacologia , Secretina/farmacologiaRESUMO
The myoelectric activity of the sphincter of Oddi was studied both in the fasted and fed states and following administration of gastrointestinal hormones. Electromyographic recordings were obtained from 21 opossums in the fasted state and following administration of 20 Cal/kg of fat, protein, carbohydrate or isocaloric mixture of these three aliments. The proximal segment of the sphincter of Oddi generated spontaneous spike potentials that migrated to the distal segment of the sphincter. The frequency of spike potentials correlated with the migrating myoelectric complex in the duodenum. Following feeding, the migrating myoelectric complex was abolished and substituted by a fed pattern. The duration of the fed pattern and the frequency of spike potentials depended on the kind of aliment. Cholecystokinin and pentagastrin increased and glucagon and secretion decreased the frequency of spike potentials in the sphincter of Oddi. It is concluded from these studies that the sphincter of Oddi may play an important role in controlling the time and rate of biliary drainage into the duodenum.
Assuntos
Ampola Hepatopancreática/fisiologia , Hormônios Gastrointestinais/farmacologia , Motilidade Gastrointestinal , Esfíncter da Ampola Hepatopancreática/fisiologia , Potenciais de Ação , Animais , Colecistocinina/farmacologia , Dieta , Eletromiografia , Glucagon/farmacologia , Pentagastrina/farmacologia , Secretina/farmacologiaRESUMO
In collagenase isolated rat pancreatic islets, CCK-PZ, SHG, secretin and glucagon stimulated the accumulation of cAMP, in physiological ranges. The resulting increment of cAMP showed a good correlation with insulin release stimulated by either glucagon or secretin, but not by SHG or CCK-PZ. In the same system, 14CO2 production from glucose-U-14C was significantly increased by either SHG or CCK-PZ. The results presented in this report are compatible with the hypothesis that insulin release by gastrointestinal hormones may be mediated by cAMP in the B-cell in the case of either glucagon or secretin; whereas, in the case of either SHG or CCK-PZ, it may presumably be mediated by an unknown mechanism in glucose metabolism, other than c-AMP.