Plasma Gastrin Concentrations Research Articles

Diagnostic significance of plasma gastrin concentration for the diagnosis of type 1 abomasal ulcer in water buffalo: A preliminary case control study

The type 1 abomasal ulcer (AU1) does not have specific clinical signs, so there is a need to identify some early biochemical markers for its diagnosis in cattle and buffaloes. The plasma gastrin is reported to reflect the gastric mucosa damage but its utility for the diagnosis of AU1 in buffaloes has not been evaluated. The objective of this study was to investigate the test performance of plasma gastrin to distinguish between healthy buffaloes and the buffaloes with AU1. Twenty-three buffaloes with AU1 and six buffaloes without any abomasal ulcer were used. The blood samples were collected from buffaloes, slaughtered in a buffalo specific slaughterhouse for estimation of the plasma gastrin. After slaughter the abomasa were examined for the presence of AU1 and the blood samples were collected for estimation of plasma gastrin. The mean plasma gastrin concentration of the ulcer-positive buffaloes was significantly (P<0.05) higher than the ulcer-negative buffaloes. The receiver operating characteristic curve analysis suggested that the optimal value of plasma gastrin for the diagnosis of AU1 was 106.2 pg/mL. This preliminary work suggests that plasma gastrin could be a valid diagnostic test for the detection of AU1 in the buffaloes. The sensitivity, specificity, positive predictive value and negative predictive value of the plasma gastrin to diagnose AU1 in the buffaloes were 78.3, 100, 100 and 69.9 pg/mL, respectively.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.

Influence of weaning management on gastritis incidence in foals

This study evaluated the incidence of gastritis in foals subjected to different weaning management methods. Sixteen crossbreed foals [230 ± 35 kg], were enrolled in an experiment with a randomized block design. After weaning, foals were housed in either individual pens or a group pen. Gastritis in the foals was evaluated through gastroscopy. Data were submitted to analysis of variance by the non-parametric Friedman test at 0.05 significance level. Before weaning, gastritis was observed in 87.5% of the foals, and the scores for the number of gastric lesions were 2.10 and 1.56 for foals housed in group and individual pens, respectively. After weaning, the scores for the number of gastric lesions were 1.75 and 1.25 for foals housed in group and individual pens, respectively. For the intensity of gastric lesions, the average scores observed before weaning were 3.31 and 1.37 for foals housed in groups and individual pens, respectively. After weaning, the scores for the intensity of gastric lesions were 1.93 and 1.00 for foals housed in group and individual pens, respectively. The intensity of the gastric lesions decreased when comparing foals prior to weaning and after weaning, regardless of the management system (P < .05). The number of lesions was not significantly different but tended to decrease after weaning. Differences in plasma cortisol concentrations were observed between samples collected on the weaning date and after weaning (P < .05). No differences were detected in plasma gastrin concentration. In conclusion, gastritis in foals can be observed before weaning, which contributes to a decreased gastric lesion incidence.

Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis

BackgroundIt is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown.MethodsAdult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis.ResultsWe found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection.ConclusionOur data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.

Sacubitril/valsartan increases postprandial gastrin and cholecystokinin in plasma

AimsNeprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and resultsNine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P = 0.004) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96).ConclusionOur study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

Gastrin secretion in normal subjects and diabetes patients is inhibited by glucagon-like peptide 1: a role in the gastric side effects of GLP-1-derived drugs?

Background: Randomized and controlled trials of glucagon-like peptide-1 (GLP-1) derived drugs have shown that the most frequent adverse symptoms are gastrointestinal. Some of the side effects such as dyspepsia, nausea and upper abdominal pain may well be of gastric origin. Since the antral hormone gastrin regulates gastric secretion of acid and enzymes and contributes to the regulation of gastric motility, we examined the effect of GLP-1 on the secretion of gastrin in normal subjects and diabetes patients.Method: Plasma was sampled from ten healthy subjects and ten patients with diabetes mellitus type 1 with glucose clamped between 6 and 9 mM. GLP-1 or saline were infused for 4 h during and after a meal. Plasma concentrations of gastrin and GLP-1 were measured using specific radioimmunoassays.Results: Basal plasma concentrations of gastrin were similar in controls and patients. After the meal, the gastrin concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of gastrin significantly, most pronounced in the diabetes patients.Conclusions: The results show that GLP-1 infusion suppresses the postprandial secretion of gastrin in normal subjects and even more so in the diabetes patients. The results may therefore shed further light on the upper gastrointestinal side effects of GLP-1-derived drugs in diabetic patients.

Effects of Short-Distance Recreational Mushing on Oxytocin, Gastrin, and Creatinine Kinase in Sled Dogs

ABSTRACTA considerable increase in creatinine kinase (CK) activity and gastrin hormone due to exercise has been observed in sled dogs during endurance mushing races; however, there have been no studies on sled dogs during recreational mushing. Although oxytocin hormone is involved in social behaviors and empathy, it has not been studied in sled dogs. This study aimed to assess changes in plasma CK activity, and gastrin and oxytocin concentrations in adult sled dogs used in touristic mushing in North Patagonia, Argentina. Blood samples were collected before, during, and after the winter season of 2017. Creatinine kinase activity measurement was done using an enzymatic assay. Hormone analyses were performed using commercial Enzyme-Linked InmunoSorbent Assay kits. Results showed an expected two-fold increase in CK activity during the winter, with recovering basal values after winter (< 400 UI/L), low and stable levels of gastrin (9.4 ± 8.8 pg/mL), and a slight increase in oxytocin (23%) after mushing activities. No evidence indicated gastrin alterations or muscular damage from touristic mushing, but an oxytocin increase would indicate a stimulation of the brain reward system.

Effect of dietary fiber and diet particle size on nutrient digestibility and gastrointestinal secretory function in growing pigs.

Reduction of diet particle size (PS) increases feed efficiency due to an increase in the apparent total tract (ATTD) of GE. However, other effects of PS on the gut secretory function are not known. Therefore, the objective of this experiment was to measure the effect of diet composition (DC) and PS on nutrient digestibility, gastrointestinal hormones, total bile acids (TBA), total cholesterol and glucose concentrations in plasma of finishing pigs ( = 8/diet). Pigs were fed finely (374 ± 29 µm) or coarsely (631 ± 35 µm) ground corn-soybean meal (CSB), CSB + 35% corn dried distillers' grains with solubles (DDGS), and CSB with 21% soybean hulls (SBH) diets for 49 d. Diet composition, nutrient digestibility, along with fasting plasma concentrations of gastrin, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), TBA, cholesterol, and glucose were measured. Fine ground diets had greater ( < 0.05) ATTD of GE as well as greater ( < 0.05) ME than coarse ground diets independent on the DC. Fine ground diets also had greater ( < 0.05) ATTD of DM, N, ether extract, and NDF, independent of DC. A decrease in PS also caused an increase ( < 0.05) in ATTD of N, K, and S, but it did not affect ATTD of Ca, P, or Na. The DC and PS affected plasma gastrin, insulin and TBA but not GIP, GLP-1, glucose, and cholesterol. Gastrin concentration was greater ( < 0.05) in pigs fed coarse DDGS compared with feeding coarse CSB and SBH diets. Insulin concentration of pigs fed CSB was greater ( < 0.01) in pigs fed fine compared with coarse DDGS, and was greater ( < 0.05) in coarse compared with fine SBH diets. Pigs fed DDGS had greater ( < 0.05) TBA than those fed SBH and fine CSB diets. Gastrin, insulin, TBA and cholesterol tended ( < 0.10), or correlated ( < 0.05) with P, K and Fe intake. Insulin, TBA, and cholesterol were correlated ( < 0.05) with Na and S intake. In conclusion, a decrease in diet PS increases the ATTD of nutrients independently of DC, while mineral intake affects gastrointestinal secretion of hormones with potential metabolic impacts. Plasma insulin and glucose concentrations were correlated with DM intake, and glucose was associated with lipid and protein intake. Diet energy, nutrient digestibility, and plasma gastrin, insulin and TBA concentrations were affected by DC and PS.

Effects of acupuncture at acupoints at different time points on occurrence of postoperative nausea and vomiting in patients undergoing radical rectal cancer operation: determination of plasma gastrin concentration

Objective To investigate the effects of acupuncture at acupoints at different time points on the occurrence of postoperative nausea and vomiting ( PONV ) in patients undergoing radical rectal cancer operation.Methods One hundred and thirty ASA Ⅰ - Ⅲ patients,aged 40-59 yr,with body mass index of 20-25 kg/m2,scheduled for elective radical rectal cancer operation,were randomly divided into 5 groups ( n =25 each):control group ( group Ⅰ ),treatment with the conventional drug group (group Ⅱ ),preoperative acupuncture group ( group Ⅲ ),acupuncture during operation group (group Ⅳ ),and postoperative acupuncture group (group Ⅴ ).Granisetron 3 mg was injected intravenously before the end of the operation in group Ⅱ.Acupuncture was performed at 30 min before induction of anesthesia,at skin incision and at the end of operation in groups Ⅲ,Ⅳ and Ⅴ respectively.Bilateral Neiguan ( PC6 ),Hegu ( LI4 ),Zhigou ( SJ6 ),and Quchi ( LI11 ) acupoints were selected in groups Ⅲ,Ⅳ and Ⅴ.Acupuncture stimulation lasted for 30 min.Blood samples were collected from the peripheral vein after admission to the operating room (T0),at 1 h after skin incision (T1),at the end of operation (T2 ),and at 24 h after operation (T3) to determine the plasma gastrin concentration.The occurrence of PONV was recorded within 2 h after operation,during 2-6 h,6-12 h and 12-24 h after operation,and within 24 h after operation.Results Compared with group Ⅰ,the incidence of PONV within 2 and 24 h after operation,and the plasma gastrin concentration at T3 were significantly decreased in groups Ⅱ and Ⅲ ( P ＜ 0.05),and no significant change was found in the indexes mentioned above in groups Ⅳ and Ⅴ (P ＞ 0.05).Compared with group Ⅱ,the plasma gastrin concentration at T3 was significantly decreased in group Ⅲ,the incidence of PONV within 2 and 24 h after operation was significantly increased in groups Ⅳ and Ⅴ ( P ＜ 0.05).Compared with group Ⅲ,the incidence of PONV within 2 and 24 h after operation,and the plasma gastrin concentration at T3 were significantly increased in groups Ⅳ and Ⅴ ( P ＜ 0.05 ).Conclusion Preoperatvie acupuncture at acupoints can decrease the occurrence of PONV in patients undergoing radical rectal cancer operation,the efficacy is similar to that of the conventional drugs,and the decreased concentration of the plasma gastrin after operation is involved in the mechanism. Key words: ELECTROACUP ANESTHESIA; Gastrins; Postoperative nausea and vomiting

Effects of Histamine H2‐receptor Antagonists on Human Plasma Levels of Motilin, Gastrin, Secretin and Somatostatin

The effects of the histamine H2-receptor antagonists ranitidine, nizatidine, cimetidine and famotidine, on plasma levels of motilin, gastrin, secretin and somatostatin were studied in five healthy volunteers. Peak plasma motilin levels (62 and 44.4 pg mL−1) were achieved 60min after administration of nizatidine and ranitidine, respectively (P < 0.01 vs placebo), and returned to baseline levels within a further 60–120 min. Plasma gastrin concentrations increased 60–120 min after administration of nizatidine (P < 0.05 vs placebo). The physiological release of plasma secretin was reduced by administration of histamine H2-receptor antagonists (P < 0.05 vs placebo). Plasma somatostatin levels were not significantly changed. The motilin-increasing effects of nizatidine and ranitidine may alter gastrointestinal motility.

The Zollinger–Ellison Syndrome and Mismeasurement of Gastrin

Zollinger-Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of gastrin in plasma. We examined the accuracy of commercial kits to measure gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or false-high concentrations of gastrin. Failure to diagnose gastrinomas has serious consequences. Four kits found false-low concentrations of gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only gastrin-17. Three kits found false-high concentrations of gastrin, because the reagents had increased reactions to sulfated gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of gastrin. Seven of 12 tested commercial kits inaccurately measure plasma concentrations of gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of gastrinoma based on lack of specificity of assays for gastrin results in ineffective or inappropriate therapy for patients with ZES.

Ghrelin and gastrin in advanced gastric cancer before and after gastrectomy

To investigate plasma ghrelin, gastrin and growth hormone secretagogue receptor (GHS-R) expression in advanced gastric cancer (GC) before and after resection. Seventy subjects in whom endoscopy of the upper gastrointestinal tract was performed in the Department of General Surgery at Cracow University during the past decade: (1) 25 patients with GC associated with Helicobacter pylori (H. pylori) infection; (2) 10 patients with GC 4-5 years after (total or subtotal) gastrectomy; (3) 25 healthy H. pylori-negative controls, matched by age and BMI to the above two groups; and (4) 10 GC patients 4-5 years after total gastrectomy. Ghrelin and gastrin plasma concentrations were measured by specific radioimmunoassay under fasting conditions and postprandially at 60 and 90 min after ingestion of a mixed meal. GHS-R expression was examined in biopsy samples from intact healthy mucosa and GC tissue using semi-quantitative reverse transcription-polymerase chain reaction. In healthy controls, fasting plasma ghrelin levels were significantly elevated and declined markedly at 60 and 90 min after a mixed meal. The concomitant enhanced ghrelin, GHS-R and gastrin expression in GC tissue over that recorded in intact mucosa, and the marked rise in plasma gastrin in these subjects under fasting conditions indicate the role of these hormonal factors in GC formation. Fasting plasma levels and postprandial response of ghrelin and gastrin appear to be inversely correlated in healthy subjects. Feeding in the controls resulted in a significant fall in plasma ghrelin with a subsequent rise in plasma gastrin, but in H. pylori-positive GC patients submitted to total or distal gastrectomy, feeding failed to affect significantly the fall in plasma ghrelin that was recorded in these patients before surgery. Fasting ghrelin concentrations were significantly lower in patients 4-5 years after total gastrectomy compared to those in healthy controls and to these in GC patients before surgery. Elevated plasma gastrin and suppression of fasting ghrelin in patients with GC suggest the existence of a close relationship between these two hormones in gastric carcinogenesis.

Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells

Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biopsies from subjects with elevated plasma gastrin, the abundances of PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared with subjects with plasma concentrations in the reference range. In patients with hypergastrinemia due to autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1, uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy. Immunohistochemistry revealed localization of PAI-1 to parietal cells and enterochromaffin-like cells in micronodular neuroendocrine tumors in hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI-1-luciferase promoter-reporter construct transfected into AGS-G(R) cells. There was time- and concentration-dependent increase of PAI-1-luciferase expression in response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways. In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-G(R) cell migration and invasion, and small interfering RNA treatment increased responses to gastrin. We conclude that elevated plasma gastrin concentrations are associated with increased expression of gastric PAI-1, which may act to restrain gastrin-stimulated cell migration and invasion.

Pharmacokinetics of enteric‐coated cysteamine bitartrate in healthy adults: a pilot study

Cysteamine bitartrate is taken lifelong, every 6 h and for the treatment of cystinosis. Recent studies using cysteamine for for other diseases such as neurodegenerative disorders adopt the same dosing regimen for cysteamine. Regular cysteamine bitartrate (Cystagon) may cause upper gastrointestinal symptoms in some patients. This is the only study that provides pharmacokinetic data for cysteamine delivered in an enteric-release preparation in normal subjects. EC-cysteamine is very well tolerated and does not cause increased gastrin concentrations, even at relatively high doses. EC-cysteamine at the higher dose results in better drug uptake as measured by Cmax and AUC and is more likely to be effective. Cysteamine bitartrate (Cystagon) is the approved treatment for cystinosis. Poor compliance and patient outcome may occur because the drug needs to be taken every 6 h and in some patients causes gastrointestinal symptoms due to hypergastrinaemia. A formulation of cysteamine requiring twice daily ingestion would improve the quality of life for these patients. This study compares the pharmacokinetics and gastrin production following cysteamine bitartrate non-enteric-coated and cysteamine bitartrate enteric-coated in normal healthy subjects. Enteric-coated cysteamine was prepared. Following single doses of cysteamine bitartrate non-enteric-coated 450 mg and cysteamine bitartrate enteric-coated 450 mg and 900 mg, serial plasma cysteamine and gastrin concentrations were measured. Two subjects also received cysteamine bitartrate non-enteric-coated 900 mg. Gastrointestinal (GI) symptoms were recorded. Six healthy adults (mean age 20.7 years, range 18-24 years; mean weight 59.3 kg) received drug. All post-dose gastrin concentrations were within the normal range (<100 pg ml(-1)). The tmax following cysteamine bitartrate non-enteric-coated (mean and SD is 75+/-19 min) was shorter than cysteamine bitartrate enteric-coated (220+/-74 min) (P=0.001), but only the Cmax and AUC estimates following 900 mg cysteamine bitartrate enteric-coated were significantly greater than any of the other preparations or doses (P<0.05). One patient had GI symptoms following both 900 mg cysteamine bitartrate non-enteric-coated and cysteamine bitartrate enteric-coated. Although patient numbers were low, single high doses of cysteamine bitartrate enteric-coated were better tolerated than similar doses of cysteamine bitartrate non-enteric-coated in the healthy subjects and all had normal gastrin concentrations. The delayed tmax following cysteamine bitartrate enteric-coated suggested that the cysteamine was released enterically.

Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia

BackgroundGastrointestinal (GI) dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK), gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility.MethodsNineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations.ResultsThere was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015) whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114). Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051) and those with autonomic neuropathy had a higher area under the curve (AUC) of gastrin compared to normal subjects (p = 0.007).ConclusionReduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

Esomeprazole reduces gastroesophageal reflux after beer consumption in healthy volunteers

Objective. Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption. Material and methods. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined. Results. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pH<4) as compared to placebo (2.6%), but gastric emptying, blood ethanol and cholecystokinin concentrations were not significantly different after esomeprazole treatment. Plasma gastrin levels were significantly (p=0.0003) higher after esomeprazole (98.6±19.7 pg/ml) than after placebo (22.7±3.8 pg/ml) before beer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo. Conclusions. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

Morphometric and immunohistochemical study of the abomasum of red deer during prenatal development

The red deer is well suited to scientific study, given its economic importance as an animal to be hunted, and because it has a rich genetic heritage. However, there has been little research into the prenatal development of the stomach of ruminants in general, and none for the red deer. For this reason, we undertook histological evaluation of the ontogenesis of the abomasum in red deer. Histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses from the initial stages of prenatal life until birth. The animals were divided for test purposes into five experimental groups: group I [1.4-3.6 cm crown-rump length (CRL); 30-60 days, 1-25% of gestation]; group II (4.5-7.2 cm CRL; 67-90 days, 25-35% of gestation); group III (8-19 cm CRL; 97-135 days, 35-50% of gestation); group IV (21-33 cm CRL; 142-191 days, 50-70% of gestation) group V (36-40 cm CRL; 205-235 days, 75-100% of gestation). In the organogenesis of the primitive gastric tube of red deer, differentiation of the abomasum took place at 67 days, forming a three-layered structure: the epithelial layer (pseudostratified), pluripotential blastemic tissue and serosa. The abomasal wall displayed the primitive folds of the abomasum and by 97 days abomasal peak areas were observed on the fold surface. At 135 days the abomasal surface showed a single mucous cylindrical epithelium, and gastric pits were observed in the spaces between abomasal areas. At the bottom of these pits the first outlines of glands could be observed. The histodifferentiation of the lamina propria-submucosa, tunica muscularis and serosa showed patterns similar to those described for the forestomach of red deer. The abomasum of red deer during prenatal life, especially from 67 days of gestation, was shown to be an active structure with full secretory capacity. Its histological development, its secretory capacity (as revealed by the presence of neutral mucopolysaccharides) and its neuroendocrine nature (as revealed by the presence of positive non-neuronal enolase cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y) were in line with the development of the rumen, reticulum and omasum. Gastrin-immunoreactive cells first appeared in the abomasum at 142 days, and the number of positive cells increased during development. As for the number of gastrin cells, plasma gastrin concentrations increased throughout prenatal life. However, its prenatal development was later than that of the abomasum in sheep, goat and cow.

Gastric Inflammation, Metaplasia, and Tumor Development in Gastrin–Deficient Mice

Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after 1 week of gastrin infusion, and wild-type mice treated for 1 month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immunohistochemistry. Selective media were used to characterize the gastric microflora. The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia.

Pre- and post-feeding plasma gastrin-17 and insulin concentrations and feed intake in female goats during different physiological stages

Gastrin (GAS) and insulin (INS) play a significant role in the regulation of feed intake, as well as in the homeorhetic adaptations to different physiological stages, nutrient supply and requirements. The aim of the study was to verify if plasma GAS and INS concentrations in adult does are affected by the physiological state, change in response to the meal and are correlated with feed intake and energy balance. Dry matter intake (DMI) and pre and post-prandial plasma concentrations of gastrin-17 and insulin were recorded in 21 female goats fed hay and different quantities of concentrate (maize grain) twice daily in different physiological states. DMI was lower during the week of oestrous activity, compared to the period of anoestrus – progressively decreasing during pregnancy and increasing during the post-partum period, without significant differences between early and late lactation. Plasma GAS concentrations were significantly affected by physiological status, being higher ( P < 0.05) during lactation than during pregnancy. Overall plasma GAS concentrations increased ( P < 0.01) from pre-feeding levels (169 ± 24 pg/ml), to 30 min after feed ingestion (185 ± 29 pg/ml). The increase occurred 10 and 20 min ( P < 0.05) after feeding, regardless of the diet composition. Both pre- and post-prandial GAS concentrations were related to DMI ( P < 0.001), but not to the energy intake. Plasma INS on the other hand was not significantly affected by the physiological status. The pre-feeding plasma INS concentration, across all physiological states, was 1.36 ± 0.32 ng/ml and increased ( P < 0.01) to 1.45 ± 0.38 ng/ml 30 min after feeding. Pre-feeding INS, but not post-prandial INS, increased with increasing proportions of maize in the diet and energy intake ( P < 0.05). Overall INS was negatively correlated ( P < 0.05) to DMI. It was concluded that cephalic reflexes are efficient stimula for both GAS and INS release in adult goats fed twice daily. Plasma GAS concentrations were related to hay intake and total DMI, thus with the volume of ingesta and presumably the time spent eating. GAS concentrations were not affected by the type of feed, nor the energy intake or the flux into the abomasum. Pre-feeding plasma INS was mainly dependent on the energy intake, while the post prandial increase was not dependent on the size or quality of the meal, or on the energy intake. Dietary manipulation and feed ingestion can thus affect the circulatory levels of these two main endocrine factors.