Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GASTROINTESTINAL HORMONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1982

Duodenal perfusion with sodium taurocholate inhibits biliary but not pancreatic secretion in man.

1. A standard duodenal perfusion technique was used to study the effects of luminally perfused sodium taurocholate on basal and stimulated biliary and pancreatic secretion and gastrointestinal hormone release in man. 2. During duodenal perfusion with sodium taurocholate alone, both basal and caerulein/secretin-stimulated bilirubin secretion were suppressed. A successive perfusion with a mixture of the bile salt and essential amino acids in combination overcame the biliary suppression and biliary secretion rose above basal levels. A further increase in bilirubin secretion was not observed in a subsequent perfusion with essential amino acids alone in these studies. 3. No inhibitory effect on basal or caerulein/secretin-stimulated trypsin secretion was observed during the bile salt perfusion; basal trypsin secretion was in fact slightly increased during a prolonged (4 h) perfusion of the bile salt. 4. During bile salt perfusion, basal bicarbonate secretion remained unchanged but caerulein/secretin-stimulated bicarbonate secretion was slightly increased. 5. Plasma levels of pancreatic polypeptide, gastric inhibitory peptide and gastrin did not change significantly during duodenal perfusion with bile salt, but plasma levels of motilin were suppressed. 6. These results support the view that bile salts in the duodenum may regulate biliary and pancreatic secretion in man and affect plasma levels of motilin.

Adult↗
PubMed2006

Central nervous system circuitry involved in the hyperinsulinism syndrome.

Raised plasma levels of insulin, glucose and glucagon are found in patients affected by 'hyperinsulinism'. Obesity, hypertension, mammary plus ovary cysts and rheumatic symptoms are frequently observed in these patients. Sleep disorders and depression are also present in most subjects affected by this polysymptomatic disorder. The simultaneous increases of glucose, insulin and glucagon plasma levels seen in these patients indicate that the normal crosstalk between A cells, B cells and D cells is disrupted. With respect to this, it is well known that glucose excites B cells (which secrete insulin) and inhibits A cells (which secrete glucagon), which in turn excites D cells (which secrete somatostatin). Gastrointestinal hormones (incretins) modulate this crosstalk both directly and indirectly throughout pancreatic and hepatobiliary mechanisms. The above factors depend on autonomic nervous system mediation. For instance, acetylcholine released from parasympathetic nerves excites both B and A cells. Noradrenaline released from sympathetic nerves and adrenaline secreted from the adrenal glands inhibit B cells and excite A cells, which are crowded with beta(2)- and alpha(2)-receptors, respectively. Noradrenaline released from sympathetic nerves also excites A cells by acting at alpha(1)-receptors located at this level. According to this, the excessive release of noradrenaline from these nerves should provoke an enhancement of glucagon secretion which will result in overexcitation of insulin secretion from B cells. That is the disorder seen in the so-called 'hyperinsulinism', in which raised plasma levels of glucose, insulin and glucagon coexist. Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome.

Animals↗
PubMed1992

Ca2+/calmodulin regulation of putrescine uptake in cultured gastrointestinal epithelial cells.

Regulation of putrescine uptake in a small intestinal crypt cell line, IEC-6 cells, was examined. Uptake of [14C]putrescine was measured throughout a normal growth curve and was found to be inversely related to growth. Kinetic analysis at low and high cell density revealed the inhibition of uptake in confluent cells was due to a five-fold reduction in Vmax of uptake, 199.5 vs. 43.1 pmol.10(5) cells-1.h-1, respectively. Three gastrointestinal hormones, gastrin, secretin, and cholecystokinin, produced partial inhibition of [14C]putrescine uptake. Conversely, treatment of quiescent cells with 5% fetal bovine serum to stimulate growth did not affect uptake. Influence of putrescine uptake on free ionized intracellular Ca2+ ([Ca2+]i) was measured by microspectrofluorometry using the Ca(2+)-sensitive fluoroprobe fura-2. Basal [Ca2+]i was calculated to be 112 nM and increased rapidly to 313 nM upon addition of 10 microM putrescine. Preventing the rise in [Ca2+]i using an intracellular Ca2+ buffer, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, decreased [14C]putrescine uptake to 29.5 +/- 5.3% of control values. 45Ca2+ flux experiments and measurement of transport in 0 Ca2+ and 0.5 mM EDTA suggested an intracellular source of calcium was mobilized during putrescine uptake. Finally, use of the putative calmodulin antagonist N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide caused a dose-dependent inhibition of [14C]putrescine uptake with 50% inhibitory concentration of approximately 7 microM. These data suggest that putrescine uptake in IEC-6 cells may be regulated by a Ca2+/calmodulin-dependent mechanism.

Animals↗
PubMed1996

[Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)].

Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. GIP consists of 42 amino acid residues which is derived by proteolytic processing of a GIP precursor. In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. Thus, GIP now is generally referred to as glucose-dependent insulinotropic polypeptide. It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). GIP exerts its biological actions by binding to its specific receptors, which appear to be coupled to G proteins. We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells.

Animals↗
PubMedDate not supplied

Physiology and pathophysiology of the lower esophageal sphincter.

The physiologic factors controlling lower esophageal sphincter (LES) function are interrelated in a complex fashion and include the autonomic nerve supply, gastrointestinal hormones, and specific characteristics of the circular smooth muscle at the esophagogastric junction. It might be expected that a defect in any of these three controlling mechanisms would result in a clinically recognizable symptom complex. Abnormalities with either high or low LES pressure have been shown to relate to these specific aspects. Studies of the effects of various foods and other agents which decrease or increase LES pressure are of therapeutic interest in relating to patients with reflux symptoms. Decreases in LES pressure occurring after fat ingestion may explain a mechanism for many cases of fatty food intolerance. Pressure decreases after chocolate ingestion, after smoking, and after alcohol all have strong therapeutic implications in patients with chronic heartburn. Gastric alkalinization will increase pressure for up to one hour in patients with basal sphincter hypotension and reflux symptoms. Recent studies with drugs that work through the cholinergic mechanism have important therapeutic considerations. Anticholinergic agents produce definite decreases in LES pressure and are to provided in treatment of patients with reflux symptoms. On the other hand cholinergic drugs such as bethanechol have been shown to increase LES pressure in normal subjects and in patients with chronic sphincter incompetence. Recently, a double-blind therapeutic trial with bethanechol in patients with chronic heartburn has indicated that this drug, when given on regular basis, is an effective adjunct to therapy in these patients.

Anemia, Pernicious↗
PubMed1999

Characterization of the carboxyl-terminal domain of the rat glucose-dependent insulinotropic polypeptide (GIP) receptor. A role for serines 426 and 427 in regulating the rate of internalization.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. In non-insulin-dependent diabetes mellitus insulin responses to GIP are blunted, possibly due to altered signal transduction or reduced receptor number. Site-directed mutagenesis was used to construct truncated GIP receptors to study the importance of the carboxyl-terminal tail (CT) in binding, signaling, and receptor internalization. Receptors truncated at amino acids 425, 418, and 405, expressed in COS-7 or CHO-K1 cells, exhibited similar binding to wild type receptors. GIP-dependent cAMP production with the 405 mutant was decreased in COS-7 cells. Maximal cAMP production in CHO-K1 cells was reduced with all truncated forms. Binding was undetectable with a receptor truncated at amino acid 400; increasing tail length by adding 5 alanines restored binding and signaling. Mutants produced by alanine scanning of residues 394-401, adjacent to transmembrane domain 7, were all functional. CT truncation by 30 or more amino acids, mutation of serines 426/427, singly or combined, or complete CT serine knockout all reduced receptor internalization rate. The majority of the GIP receptor CT is therefore not required for signaling, a minimum chain length of approximately 405 amino acids is needed for receptor expression, and serines 426 and 427 are important for regulating rate of receptor internalization.

Animals↗
PubMed1995

Molecular cloning and functional characterization of a human secretin receptor.

Secretin is a gastrointestinal hormone responsible for the regulation of bicarbonate, potassium ion and enzyme secretion from the pancreas. A cDNA encoding the human secretin receptor was isolated from a human pancreatic adenocarcinoma cell-line cDNA library using polymerase chain reaction and library screening techniques. The cDNA isolated is 1717 bp in length encoding a 440 amino acid long polypeptide. Computer analysis of the receptor indicated that it is a member of the glucagon-VIP-secretin receptor family and is a G-protein coupled receptor containing seven hydrophobic transmembrane domains. The receptor was subsequently expressed in COS-7 cells and was able to bind specifically to human secretin with high affinity as indicated by the competitive displacement assay. The human secretin receptor was found to be functionally coupled to the stimulation of adenylyl cyclase resulting in the accumulation of intracellular cAMP in a dose-dependent manner. By Northern blot analysis, a 1.8 Kb mRNA was detected in human pancreas and intestine, while weak hybridization signals were detected in human colon, kidney and lung. Functional characterization of this receptor should enhance our understanding of the physiology and pathophysiology of human secretin, its structure-function, receptor interaction and receptor tissue distribution.

Adenocarcinoma↗
PubMed1996

Pepsinogens and gastrointestinal symptoms in mountain marathon runners.

Although there are various descriptive reports concerning exercise-induced gastrointestinal distress, the role of gastrointestinal hormones and/or enzymes is not definitively established. In this study we investigated the behaviour of pepsinogens (PGI and PGII) after an endurance race performed at an altitude of 4,300 m by 13 well-trained marathon runners, with the aim to establish their interrelationship with gastrointestinal distress and with the modifications of gastrin and cortisol. The athletes showed a significant rise in gastrin (p < 0.01) and in cortisol (p < 0.01) and a significant decrease in PGI (p < 0.01) and PGII (p < 0.05) after the race. The PGI/PGII ratio presented small variations indicating that heavy exercise has less effects on PGs than those observed for gastrin. Gastrointestinal symptoms occurred in 6 athletes (46%) during the race and in 8 athletes (62%) after the race. No relationship was found between gastrointestinal symptoms and hormonal modifications after the race. A control group of 5 subjects was used: they (n = 5) did not show any significant modification of gastrin and PGs during the period spent at the above altitude, indicating that travel, altitude and acclimatization, food and beverages, do not influence the behaviour of these hormones. Conversely, they presented a significant decrease of cortisol (p < 0.05) linked to the circadian rhythm. The data of the present study indicate that the potential damage of gastrointestinal apparatus in mountain marathon runners is not related to the above mentioned hormones.

Adult↗
PubMed2002

Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism.

BACKGROUND: High-fat and high-carbohydrate diets lead to insulin resistance, gastrointestinal adaptation, and high plasma triacylglycerol concentrations. It is unclear, however, how rapidly these changes occur. OBJECTIVE: We sought to determine the effects of both high-fat and high-carbohydrate evening meals on parameters of insulin resistance, hypertriglyceridemia, and gastrointestinal hormones. DESIGN: Twelve healthy men were studied on 4 separate occasions. On 2 occasions, the subjects received a high-fat evening meal (62% of energy from fat) and on the other 2 occasions the subjects received a low-fat evening meal (16% of energy from fat). The morning after each meal the subjects were administered either an oral-fat-tolerance test or an oral-glucose-tolerance test. Plasma samples were analyzed for glucose, insulin, fatty acids, 3-hydroxybutyrate, triacylglycerol, pancreatic polypeptide, peptide YY, and cholecystokinin. Postchallenge data were analyzed by two-way analysis of variance with interaction and fasting concentrations analyzed by repeated-measures analysis of variance. RESULTS: Fasting plasma concentrations of triacylglycerol were significantly elevated 12 h after each evening meal, but fatty acid and 3-hydroxybutyrate concentrations were reduced. No effects on glucose or insulin concentrations were detected. The high-fat evening meals elevated plasma cholecystokinin concentrations, reduced fasting concentrations of pancreatic polypeptide, and had no significant effect on peptide YY concentrations. The ratio of fat to carbohydrate in the evening meal produced significant effects on plasma triacylglycerol and fatty acids during both the oral-fat-tolerance and oral-glucose-tolerance tests. CONCLUSIONS: The present study showed that the effects of high-fat and high-carbohydrate evening meals persist at least overnight and suggests that knowledge of recent dietary history is essential to the effective design of metabolic studies.

3-Hydroxybutyric Acid↗
PubMed2005

A novel, long-acting agonist of glucose-dependent insulinotropic polypeptide suitable for once-daily administration in type 2 diabetes.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with a potentially therapeutic role in type 2 diabetes. Rapid degradation by dipeptidylpeptidase IV has prompted the development of enzyme-resistant N-terminally modified analogs, but renal clearance still limits in vivo bioactivity. In this study, we report long-term antidiabetic effects of a novel, N-terminally protected, fatty acid-derivatized analog of GIP, N-AcGIP(LysPAL(37)), in obese diabetic (ob/ob) mice. Once-daily injections of N-AcGIP(LysPAL(37)) over a 14-day period significantly decreased plasma glucose, glycated hemoglobin, and improved glucose tolerance compared with ob/ob mice treated with saline or native GIP. Plasma insulin and pancreatic insulin content were significantly increased by N-AcGIP(LysPAL(37)). This was accompanied by a significant enhancement in the insulin response to glucose together with a notable improvement of insulin sensitivity. No evidence was found for GIP receptor desensitization and the metabolic effects of N-AcGIP(LysPAL(37)) were independent of any change in feeding or body weight. Similar daily injections of native GIP did not affect any of the parameters measured. These data demonstrate the ability of once-daily injections of N-terminally modified, fatty acid-derivatized analogs of GIP, such as N-AcGIP(LysPAL(37)), to improve diabetes control and to offer a new class of agents for the treatment of type 2 diabetes.

Animals↗
PubMed1991

Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa.

Anorexia nervosa (AN) is a syndrome of unknown cause characterized by voluntary starvation. Cholecystokinin has been implicated as a neuroendocrine regulatory factor in control of satiety. Relatively little information is known about gastrointestinal hormone responses to feeding in subjects with anorexia nervosa. In the present studies, we examine fasting and postprandial levels of cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in anorexia nervosa subjects and in control individuals. Results of these studies indicate that plasma CCK response to a liquid meal (Ensure Plus) in untreated AN subjects was distinctly different from that observed in healthy controls, both in terms of temporal pattern of peptide released and the amount of CCK secreted into the circulation. Peak levels of CCK release occurred at 30 min following meal ingestion in AN patients and at 60 min in control subjects. Integrated CCK release in untreated AN patients was approximately twice that measured in control individuals. Renutrition therapy was associated with reversion of the pattern of CCK release to that observed in control subjects. Plasma VIP levels were unchanged following meal ingestion in both control and anorexic subjects. In contrast, PHM levels in AN subjects were significantly greater than that observed in control individuals. The pattern of PHM release following liquid meal ingestion was similar to that observed with plasma CCK; namely, peak release of peptide was observed at 30 min which was significantly greater than corresponding control values (P less than 0.05). In conclusion, these results demonstrate distinctive differences in plasma CCK and PHM levels in response to feeding in AN subjects when compared to control individuals. These findings suggest that the earlier and greater rise in plasma CCK levels in AN subjects following meal ingestion may contribute to the abnormal sensation of satiety in this condition.

Anorexia Nervosa↗
PubMed2006

The gastroenteroinsular response to glucose ingestion during postexercise recovery.

This study examined gastrointestinal hormone and peptide responses when glucose was ingested after prolonged exercise. Six endurance-trained male athletes ran on a treadmill for 2 h at 60% VO2 max. Immediately after the run, the athletes consumed 75 g of glucose in 250 ml of water (ExGLU) or flavored water as a placebo control (ExPL). On a separate visit, the athletes rested for 2 h and then consumed glucose (ConGLU). During the first 60 min of recovery from exercise alone (ExPL), plasma vasoactive intestinal peptide (VIP), gastrin, and glucagon-like peptide-1 (GLP-1) all increased significantly, whereas glucose, insulin, and gastric inhibitory polypeptide (GIP) were unchanged from the immediate postexercise value. When glucose was ingested after exercise (ExGLU), glucose, insulin, VIP, gastrin, GLP-1, and GIP were all increased (P < 0.01). However, when glucose was ingested after resting for 2 h (ConGLU), VIP levels were unaffected, although glucose, insulin, gastrin, GLP-1, and GIP levels increased (P < 0.05). The plasma glucose response was greater (P < 0.03) and the plasma insulin response lower (P < 0.004) during ExGLU compared with ConGLU. There was a significantly higher (P < 0.01) VIP response during the initial period of recovery in ExGLU than there was with both ExPL and ConGLU. Plasma VIP showed a modest negative correlation with circulating glucose (r = -0.35, P < 0.03) and insulin (r = -0.37, P < 0.03) during the ExGLU recovery period. In summary, when glucose is ingested after prolonged exercise, there is mild insulin resistance and a corresponding rapid transitory increase in plasma VIP. These data suggest that VIP may play an important glucoregulatory role when glucose is ingested during the immediate postexercise recovery period.

Administration, Oral↗
PubMed1992

Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type.

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that primarily function as neurotransmitter and gastrointestinal hormone, respectively. Previous functional and binding data have indicated the existence of at least three distinct receptor types, Y1, Y2, and Y3, for NPY and/or PYY in mammals. We describe here a human Y1 cDNA clone, hY1-5, isolated from a fetal brain library. The human Y1 receptor consists of 384 amino acids and has seven putative transmembrane domains like other members of the G-protein-coupled superfamily of receptors. In the region spanning the transmembrane domains, the Y1 receptor displays 29% sequence identity to human tachykinin receptors, but it only shows 21% and 23% homology with proposed bovine (LCR1) and Drosophila (PR4) NPY receptor clones, respectively. Northern blot analysis of a human neuroblastoma cell line, SK-N-MC, previously used by many investigators as a model system for studies on the Y1 receptor, revealed a single 3.5-kilobase mRNA species. Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y1 receptor is associated with NPY/PYY-evoked vasoconstriction. When expressed in COS1 cells, hY1-5 conferred specific 125I-PYY binding sites with displacement patterns characteristic of the Y1 receptor, i.e. PYY greater than or equal to NPY greater than or equal to [Leu31,Pro34]NPY much greater than NPY2-36 greater than C2NPY greater than pancreatic polypeptide greater than NPY13-36 greater than NPY18-36. Moreover, in the Y1 receptor-transfected COS1 cells, but not in type 1 angiotensin II receptor-transfected control cells, NPY and PYY accelerated 45Ca2+ influx and inhibited forskolin-stimulated cAMP accumulation, both phenomena being characteristic of the mammalian Y1 receptor.

Amino Acid Sequence↗
PubMed2000

GIP biology and fat metabolism.

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), is synthesized and released from the duodenum and proximal jejunum postprandially. Its release depends upon several factors including meal content and pre-existing health status (ie. obesity, diabetes, age, etc.). It was initially discovered and named for its gastric acid inhibitory properties. However, its more physiologically relevant role appears to be as an insulinotropic agent with a stimulatory effect on insulin release and synthesis. Accordingly, it was later renamed glucose-dependent insulinotropic polypeptide because its action on insulin release depends upon an increase in circulating levels of glucose. GIP is considered to be one of the principle incretin factors of the enteroinsular axis. The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. GIP receptor mRNA is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, suggesting it may have other functions in addition to the ones mentioned above. An overactive enteroinsular axis has been suggested to play a role in the pathogenesis of diabetes and obesity. In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids into triglycerides, (3) increase insulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. In addition, although controversial, lipolytic properties of GIP have been proposed. The mechanism of action of GIP-induced effects on adipocytes is unknown, and it is unclear whether these effects of GIP on adipocytes are direct or indirect. However, there is now evidence that GIP receptors are expressed on adipocytes and that these receptors respond to GIP stimulation. Given the location of its release and the timing of its release, GIP is an ideal anabolic agent and expanding our understanding of its physiology will be needed to determine its exact role in the etiology of diabetes mellitus and obesity.

Adipocytes↗
PubMed1996

Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog.

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.

Adaptation, Physiological↗
PubMed1999

Peptide YY inhibits growth of human breast cancer in vitro and in vivo.

BACKGROUND: Hormonal manipulation is important in the treatment of breast cancer. Gastrointestinal hormones may have antiproliferative effects on malignancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppresses growth of, and levels of, intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma. We hypothesized that PYY would inhibit growth of breast cancer. MATERIALS AND METHODS: MCF-7 human breast infiltrative ductal carcinoma cells in 96-well plates were treated with PYY at 1.25 pmol/mcl. Control wells received an equal volume of bovine serum albumin to mimic experimental conditions. In vitro survival was determined by MTT assays, which reflect cell viability by measuring mitochondrial NADH-dependent dehydrogenase activity. MCF-7 cells in six-well plates were treated with PYY or albumin as described above. Intracellular cAMP levels in cell lysates were determined with a tritiated cAMP assay. One million MCF-7 cells were injected into mammary fat pads of 20 female athymic nude mice. Pellets releasing PYY at 400 pmol/kg/h were placed subcutaneously in 10 mice 24 h prior to cell inoculation. Tumors were harvested after 21 days, weighed, and measured with vernier calipers. RESULTS: PYY reduced in vitro growth by 40% (P < 0.001). Intracellular cAMP levels in PYY-treated cells were 62.4% less than those of controls (P < 0.001). Tumors from control mice weighed twice as much as those from PYY-treated mice (P < 0.006); volume of PYY-exposed tumors was one-third that of controls (P < 0.005). CONCLUSIONS: PYY inhibits growth of breast cancer in vitro and in vivo and may be of benefit in the treatment of this malignancy. The reduction in intracellular cAMP levels may contribute to the observed suppression of cell proliferation.

Animals↗
PubMed1990

Localization of chromogranin A-immunoreactivity in bovine gastrointestinal endocrine cells with special reference to Grimelius silver stain.

Immunohistochemical studies of the gastrointestinal tract were carried out to characterize the cells exhibiting immunoreactivity for chromogranin A (CGA), a glycosylated protein primarily found in secretory granules of the adrenal medulla. Double immunostaining for gastrointestinal hormones and CGA revealed that in the bovine gastrointestinal tract CGA immunoreactivity occurs in mucosal epithelial cells containing gastrin, glucagon, substance P or motilin, but not in those containing somatostatin. Combined staining with anti-CGA serum and Grimelius' silver demonstrated frequent association of the two stains in a variety of endocrine cells. However, intracellular distribution of the two stains was different: CGA-immunoreactivity was detected in both supra- and infranuclear cytoplasm, whereas Grimelius' silver was mostly localized in the infranuclear region. These results suggest that CGA is the target of Grimelius' silver, as postulated recently (Rindi et al., 1986), but that some subcellular structure-related modification of molecules such as sialation is necessary for the positive Grimelius reaction.

Animals↗