Serum Gastrin Concentrations Research Articles

Effects of Preoperative Anxiety on Gastric Fluid Acidity and Volume

The aim of this study was to evaluate the effect of preoperative anxiety on the gastric pH and volume. We studied 96 female patients aged 16-60 yr who underwent elective gynecological surgery. We classified the subjects into 2 groups, those presenting preoperative anxiety scores using visual analogue scale (VAS, 0-10) less than 5 (L-group, n=59), and those with 5 and more (H-group, n=37). Immediately after tracheal intubation, gastric contents were aspirated using a 14-F multiorifice nasogastric tube. The gastric acidity and volume of the two groups were not statistically different. Mean pH were 3.0±1.8 and 3.0±2.0 in each group (L-group and H-group) and mean gastric volume (mL) were 15.3±11.7 and 11.8±11.8, respectively. Nine (15.3%) patients in the L-group were considered to be 'at risk i.e. gastric pH <2.5 and volume >25 mL' and one patient (2.7%) in the H-group (p<0.05). The mean serum gastrin concentrations in both groups were similar (21.6±9.8 vs. 20.2±11.0 pg/mL). The pH and volume of preoperative gastric contents were not correlated with the preoperative anxiety. The results suggest that a low level of preoperative anxiety can be considered a risk factor for aspiration pneumonitis.

FIRST DAY EFFECTS OF RABEPRAZOLE ON NOCTURNAL ESOPHAGEAL AND REGIONAL INTRAGASTRIC PH

Purpose: Proton pump inhibitors decrease gastric acid secretion, increase intragastric pH and relieve symptoms of gastroesophageal reflux disease (GERD). Many patients with acid/peptic disorders, such as GERD, are symptomatic at night. AIM: 1) Determine the effects of rabeprazole on nocturnal esophageal and intragastric pH profiles on the first and eighth day of treatment. 2) Correlate the effects on intragastric pH with serum gastrin concentration. Methods: Ten normal subjects underwent two eight-day treatment sessions with morning placebo or rabeprazole 20 mg qd, in a randomized double-blind cross-over study design separated by 2 week washout period. Esophagogas-tric pH monitoring studies were performed on days 1 and 8 of each treatment. Esophageal pH was measured 2 cm above the LES and gastric pH at 7, 12, and 17 cm distal to the esophageal pH probe. Fasting blood sample was obtained for serum gastrin measurement on the morning after each 24 hour recording. Results: During the first night (midnight to 8 am) after placebo administration, the median gastric pH was 1.3 ± 0.2, without significant regional differences. Rabeprazole significantly increased the gastric pH on the first night of administration to 3.5 ± 0.6; p <0.01). On the eighth night of administration, rabeprazole continued to increase gastric pH to 3.9 ± 0.6 (p <0.01) compared to placebo. There was a slight, but significant, increase in serum gastrin from 42 ± 6 with placebo to 85 ± 28 pg/ml on day 1 and 62 ± 8 pg/ml on day 8 of rabeprazole administration. The distal gastric pH correlated with the serum gastrin level (r = 0.423; p = 0.009). Conclusions: Rabeprazole, at 20 mg po qd, significantly elevated nocturnal gastric pH on the first day of treatment to levels that are sustained for the first week. There were no regional intragastric differences in rabeprazole's action in increasing nocturnal intragastric pH. The increase in gastric pH with rabeprazole is associated with an acute doubling (day 1) and a small rise in serum gastrin at day 8.

PPARα agonists stimulate progastrin production in human colorectal carcinoma cells

The three subtypes of peroxisome proliferator activated-receptors (PPARα, δ and γ) control the storage and metabolism of fatty acids. Treatment of rats with the PPARα ligand ciprofibrate increases serum gastrin concentrations, and several lines of evidence suggest that non-amidated gastrins act as growth factors for the colonic mucosa. The aim of the present study was to investigate the expression of PPARs and the effect of PPAR ligands on gastrin production and cell proliferation in human colorectal carcinoma (CRC) cell lines. mRNAs for all three PPAR subtypes were detected by PCR in all CRC cell lines tested. The concentrations of progastrin, but not of glycine-extended or amidated gastrin, measured by radioimmunoassay in LIM 1899 conditioned media and cell extracts were significantly increased by treatment with the PPARα ligand clofibrate. Similar increases in progastrin were seen following treatment with the PPARα ligands ciprofibrate and fenofibrate, but not with bezafibrate, gemfibrozil or Wy 14643. The PPARγ agonist rosiglitazone had no significant effect on progastrin production. The PPARα ligand clofibrate also stimulated proliferation of the LIM 1899 cell line. We conclude that some PPARα ligands increase progastrin production by the human CRC cell line LIM 1899, and that clofibrate increases proliferation of LIM 1899 cells. These studies have revealed a relationship between PPARs and gastrin, two regulatory molecules implicated in the pathogenesis of CRC.

Clinical significance of serum gastrin levels in patients with colorectal cancer

An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

Clinical significance of serum gastrin levels in patients with colorectal cancer.

An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

Plasma Vitamin B-12 Concentrations in an Elderly Latino Population Are Predicted by Serum Gastrin Concentrations and Crystalline Vitamin B-12 Intake

The prevalence of vitamin B-12 deficiency increases with age, probably resulting from malabsorption of food-bound B-12 secondary to gastric atrophy. On the basis of this assumption, the Institute of Medicine (IOM) recommends those aged >50 y consume crystalline vitamin B-12. There is limited information on the prevalence of gastric atrophy in the elderly and whether the IOM recommendation would be effective. The objective of this study was to assess predictors of vitamin B-12 status and their interactions in free-living elderly. Individuals (n = 57) with deficient plasma vitamin B-12 (p-B12 < 148 pmol/L) were compared with 68 individuals with marginal p-B12 (148-221 pmol/L) and 52 with normal p-B12 (>221 pmol/L) in a cross-sectional sample (n = 1546) of elderly (>60 y) Latinos in California. Associations were examined among p-B12 and serum gastrin, vitamin B-12 intake from food and crystalline sources, and medications that putatively affect vitamin B-12 absorption. Serum gastrin was elevated, indicating gastric atrophy, in 48% of participants with deficient p-B12, 23% with marginal p-B12 and 21% of normal p-B12 participants, and was a significant predictor of deficient p-B12 and high plasma homocysteine (p-tHcy). Median total vitamin B-12 intake exceeded recommendations and was similar among status groups. Crystalline vitamin B-12 intake in the normal p-B12 group was higher than in the deficient p-B12 group (P < 0.01), and tended to be higher than the marginal group (P = 0.07). When serum gastrin was elevated, p-B12 was predicted by crystalline vitamin B-12, but not by intake of vitamin B-12 from food. Elevated serum gastrin was highly prevalent and predicted vitamin B-12 depletion. Crystalline vitamin B-12 intake predicted p-B12 in individuals with elevated serum gastrin, supporting IOM recommendations to increase consumption of crystalline vitamin B-12.

Impact of CagA status on serum gastrin and pepsinogen I and II concentrations in Japanese children with Helicobacter pylori infection.

The study aimed to determine the association between cytotoxin-associated gene product (CagA), serum gastrin and pepsinogen levels in Japanese children infected with Helicobacter pylori. Three hundred children were enrolled in the study. H. pylori infection was assessed using an enzyme-linked immunosorbent assay, and CagA status was assessed using immunoblotting. Serum gastrin and pepsinogen concentrations were measured by radioimmunoassay. H. pylori seroprevalence was 12.3% (37/300) and CagA status was identified in 28/37 H. pylori-seropositive children (75.7%). Serum pepsinogen I and II levels were significantly higher in CagA-seropositive than CagA-seronegative children with H. pylori infection. There was no significant relationship between CagA seropositivity and serum gastrin levels. In conclusion, CagA status has a significant impact on serum pepsinogen levels, possibly through enhanced gastric mucosal inflammation.

Rat stomach ECL cells: mode of activation of histidine decarboxylase

Histidine decarboxylase (HDC) occurs in ECL cells in the oxyntic mucosa of rat stomach. It is activated by gastrin. Refeeding of fasted rats or treatment with the proton pump inhibitor omeprazole promptly raised the serum gastrin concentration and consequently the HDC activity and the HDC protein content of the oxyntic mucosa. The food- and omeprazole-induced increase in HDC mRNA expression in the oxyntic mucosa was modest by comparison. Blockade of translation (cycloheximide) but not transcription (actinomycin D) prevented the postprandial rise in HDC activity. The half-life of HDC activity (after blockade of translation) was 94 min in omeprazole-treated rats and 55 min in fasted controls. The rate of enzyme synthesis was estimated to be 15 times higher in omeprazole-treated rats than in fasted controls. Inhibition of histamine uptake into ECL-cell granules by reserpine, a blocker of the vesicular monoamine transporter type-2, lowered the HDC activity and prevented the gastrin-induced HDC activation. We suggest that HDC activation reflects enhanced transcription, translation and/or posttranslational enzyme activation as well as stabilization, and that a high cytosolic histamine concentration suppresses HDC activation.

Acid inhibitory potency of twice a day omeprazole is not affected by eradication of Helicobacter pylori in healthy volunteers.

The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. We undertook 24-hour pH-metry in 12 H. pylori-positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH >or= 3, as well as increasing the area under the H+ concentration-time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL-1alpha, IL-8, IL-13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H+ concentration-time curve 'without omeprazole' minus 'with omeprazole', when comparing 'after' versus 'before' eradication of H. pylori. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity 'with' versus 'without' omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.

Predictors of Cobalamin Deficiency in Guatemalan School Children: Diet, Helicobacter pylori, or Bacterial Overgrowth?

ABSTRACTObjectivesThe authors investigated whether low vitamin B12 intake, impaired gastric function, Helicobacter pylori infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children.MethodsThe plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and H. pylori and bacterial overgrowth were diagnosed using 13C‐urea and 13C‐xylose breath tests, respectively.ResultsH. pylori infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with H. pylori infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of H. pylori infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 ± 5.2 μg/day, but intakes for 23% of children were &lt;1.8 μg/day. B12 intake from fortified snacks added an additional 0.3 ± 0.2 μg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin.ConclusionsThe specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Predictors of cobalamin deficiency in Guatemalan school children: diet, Helicobacter pylori, or bacterial overgrowth?

The authors investigated whether low vitamin B12 intake, impaired gastric function, infection, and bacterial overgrowth were risk factors for the high prevalence of cobalamin deficiency observed in Guatemalan children. The plasma cobalamin concentration of 556 school children was measured and classified as low, marginal, or adequate. In 60 children from each of these three groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine, and plasma holotranscobalamin II were measured, and usual dietary B12 intake was estimated. Serum gastrin and pepsinogen I concentrations were measured, and and bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests, respectively. infection was present in 83% (144 of 174) of children, and bacterial overgrowth was found in 25% (28 of 113). Children with infection had higher serum gastrin and pepsinogen I. There were no significant differences among the plasma cobalamin groups in the prevalence of infection, bacterial overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a significant positive correlation between serum MMA and gastrin concentrations. The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not significantly different among the plasma cobalamin groups, but it was significantly correlated with plasma cobalamin. The specific cause of cobalamin deficiency in this population remains unclear, but these results suggest that low dietary B12 intake is a risk factor and alterations in gastric secretions may also play a role.

Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenal ulcer.

The aim of this study was to clarify the pathogenesis of Helicobacter pylori-negative duodenal ulcer (DU) by investigating the meal-stimulated serum gastrin (SG) response. The subjects were 9 patients with H. pylori-negative DU, 28 H. pylori-positive DU, 11 H. pylori-positive volunteers, and 30 H. pylori-negative volunteers. Blood samples were taken before and after consumption of a test meal. The integrated 1-hr gastrin response (IGR) was taken to be the area under the SG time curve, calculated by the trapezoid method. H. pylori infection status was determined by histology, serology, and the [13C] urea breath test. The mean basal SG concentration was lower in the H. pylori-negative DU patients than in the H. pylori-positive DU patients, but an exaggerated IGR was observed in three patients (33.3%) with H. pylori-negative DU. In conclusion, our findings indicate that an exaggerated meal-stimulated gastrin response may contribute to the pathogenesis of H. pylori-negative DU.

Lansoprazole induces mucosal protection through gastrin receptor-dependent up-regulation of cyclooxygenase-2 in rats.

Proton pump inhibitors (PPIs) are antiulcer agents that have both gastric antisecretory and mucosal protective actions. The mechanisms of PPI-induced gastric mucosal protection are not known. The present study was designed to examine the mechanism for lansoprazole-induced gastric mucosal protection in rats. Rats were given 0.5, 5, and 50 mg/kg/day lansoprazole alone or both lansoprazole (50 mg/kg/day) and a specific gastrin receptor antagonist 3R-1-(2,2-diethoxyethyl)-((4-methylphenyl)amino-carbonyl methyl)-3-((4-methylphenyl)ureidoindoline-2- one) (AG-041R) (3, 10, and 30 mg/kg/day) for 14 days. Serum gastrin concentrations were measured. The expression of cyclooxygenases (COX-1 and COX-2) in the gastric mucosa was analyzed using Western blotting and immunohistochemical staining. Another series of rats was used to examine the 1) levels of prostaglandin (PG) E2 in gastric mucosa, 2) influences of the drugs on gastric damage caused by absolute ethanol, and 3) effects of a COX-2-specific inhibitor on PGE2 in the gastric mucosa and the mucosal protection afforded by lansoprazole. Lansoprazole dose dependently increased the serum gastrin concentration and enhanced the mucosal expression of COX-2 but not that of COX-1. Lansoprazole increased gastric mucosal PGE2 and reduced gastric damage caused by ethanol. Concomitant administration of AG-041R abolished the lansoprazole-induced COX-2 expression, and increased mucosal PGE2 and mucosal protection. A specific COX-2 inhibitor blocked the lansoprazole-induced increase in mucosal PGE2 and mucosal protection. Activation of gastrin receptors by endogenous gastrin has a pivotal role in the effects of lansoprazole on COX-2 up-regulation and mucosal protection in the rat stomach.

Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells in newborn and young rats.

Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell populations in the acid-producing part of the rat stomach. While the A-like cells operate independently of gastrin, the ECL cells respond to gastrin with mobilization of histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. Gastrin is often assumed to be the driving force behind the postnatal development of the gastric mucosa in general and the ECL cells in particular. We tested this assumption by examining the oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the influence of YF476, a cholecystokinin-2 (CCK(2)) receptor antagonist. The drug was administered by weekly subcutaneous injections starting at birth. The body weight gain was not affected. Weaning occurred at days 15-22 in both YF476-treated and age-matched control rats. Circulating gastrin was low at birth and reached adult levels 2 weeks after birth. During and after weaning (but not before), YF476 greatly raised the serum gastrin concentration (because of abolished acid feedback inhibition of gastrin release). The weight of the stomach was unaffected by YF476 during the first 2-3 weeks after birth. From 4 to 5 weeks of age, the weight and thickness of the gastric mucosa were lower in YF476-treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells) were few at birth and increased gradually in number until 6-8 weeks of age (control rats). At first, YF476 did not affect the development of the pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC mRNA levels and serum pancreastatin concentration) increased slowly until weaning in both YF476-treated and control rats. From then on, there was a further increase in the ECL-cell parameters in control rats but not in YF476 rats. The postnatal development of the ghrelin cells (i.e. the A-like cells) and of the A-like cell parameters (the oxyntic mucosal ghrelin concentration and the serum ghrelin concentrations) was not affected by YF476 at any point. We conclude that gastrin affects neither the oxyntic mucosa nor the endocrine cells before weaning. After weaning, CCK(2) receptor blockade is associated with a somewhat impaired development of the oxyntic mucosa and the ECL cells. While gastrin stimulation is of crucial importance for the onset of acid secretion during weaning and for the activation of ECL-cell histamine formation and secretion, the mucosal and ECL-cell growth at this stage is only partly gastrin-dependent. In contrast, the development of the A-like cells is independent of gastrin at all stages.

Gastrinaemia, Tissue Gastrin Concentration and G Cell Density in the Antral Mucosa of Swine With and Without Gastric Ulcer of the Pars Oesophagea

Gastric ulcer of the pars oesophagea (GUPO) of the stomach, which occurs spontaneously in swine, is of unknown aetiology. Because gastrin is a potent secretagogue linked to acid secretion, this study was designed to investigate, in pigs with or without GUPO, (1) basal and food-stimulated serum gastrin concentrations, (2) the concentration of tissue gastrin, and (3) gastrin-producing (G) cell density in the antral mucosa. Sixty-four pigs (32 with, and 32 without ulceration) were studied. Antral mucosa was obtained immediately after slaughter for assessment of G-cell number and tissue gastrin concentration. The presence or absence of GUPO was not significantly associated with either of the parameters measured.

Post-Gastrectomy Osteopenia in the Rat: Bone Structure is Preserved by Retaining 10%-30% of the Oxyntic Gland Area

Background: The acid-producing part of the rat stomach (fundus) is rich in endocrine cells, i.e. ECL cells and A-like cells. The ECL cells operate under gastrin control and manufacture histamine, the chromogranin-derived peptide pancreastatin and an unidentified peptide hormone. The A-like cells produce ghrelin, a newly discovered growth hormone-releasing hormone. Surgical removal of the entire glandular stomach (gastrectomy, Gx) or the acid-producing part (fundectomy, Fx) causes osteopenia, which is striking in the calvaria. We speculate that the osteopenia develops after surgical removal of the fundus, because the fundus hosts agents that preserve bone. This study examines how much of the fundus is needed to preserve normal skull bone. Methods: Increasing portions of the fundus were resected surgically. The serum gastrin, ghrelin and pancreastatin concentrations were measured. The rats were killed after 10 weeks and the calvariae were subjected to transillumination analysis and quantitative histomorphometry. Results: Fx elevated serum gastrin in proportion to the amount of fundus resected, i.e., the more fundus that was resected, the higher the serum gastrin concentration. Serum ghrelin and pancreastatin concentrations were reduced proportionally to the amount of fundus resected. In rats subjected to 90% or 100% Fx, the calvariae displayed the anticipated pattern of bone loss. No bone loss was seen when 70% or less of the fundus was resected. Conclusions: The results of the present study indicate that 10%-30% of the fundic mucosa is needed to preserve bone. The Gx/Fx-evoked osteopenia may be explained by hormonal deficiency caused by surgically eliminating or diminishing one of the endocrine cell populations in the fundic mucosa.

A meal stimulation test in the diagnosis of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

The diagnostic value of the determination of the serum pancreatic polypeptide (PP) and gastrin concentrations after a standard meal for early diagnosis of patients with multiple endocrine neoplasia type 1 (MEN 1) is controversial. The aim of this study was to clarify this issue. Thirteen patients with MEN 1, seven healthy family members, and eight healthy controls were studied. Plasma PP and serum gastrin were measured before and after the ingestion of a standardized meal. The meal caused a statistically significant (p < 0.05) increase of both PP and gastrin in all three groups studied. Concerning PP, no statistically significant difference was observed between patients and controls. In family members, the values were significantly (p < 0.05) lower than in the other two groups. On the whole, no significant differences in gastrin levels were noted between patients and controls; in family members, the values were significantly (p < 0.05) lower than in patients. All patients who had abnormally high postprandial values of PP and gastrin also had abnormally high basal values of these two peptides. The determination of serum PP and gastrin levels after a meal stimulation test in patients with MEN 1 adds no information about the presence of pancreatic endocrine tumors over that provided by basal values of the two peptides.

Helicobacter pylori infection and fasting plasma glucose concentration

Background—Helicobacter pylori infection raises basal and meal stimulated serum gastrin concentrations and lowers iron stores, which may in turn reduce fasting plasma glucose concentrations in the population. Aim—To determine whether...

A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control

Ghrelin is a 28 a.a. gastric peptide, recently identified as a natural ligand of the growth hormone secretagogue receptor (orphan receptor distinct from the receptor for growth hormone releasing hormone). In the present study, radioimmunoassay demonstrated ghrelin-like material in the rat oxyntic mucosa with moderate amounts also in antrum and duodenum. Small amounts were found in the distal intestines and pancreas. Northern blot analysis revealed abundant ghrelin mRNA in the oxyntic mucosa. Immunocytochemistry demonstrated ghrelin-immunoreactivity in endocrine-like cells in the oxyntic mucosa. Such cells occurred in low numbers also in the antrum and duodenum. The rat oxyntic mucosa is rich in endocrine (chromogranin A/pancreastatin-immunoreactive) cells, such as the histamine-rich ECL cells (65–75% of the endocrine cells), the A-like cells (20–25%) and the D cells (somatostatin cells) (10%). The ghrelin-immunoreactive (IR) cells contained pancreastatin but differed from ECL cells and D cells by being devoid of histamine-forming enzyme (ECL cell constituent) and somatostatin (D cell constituent). Hence, ghrelin seems to occur in the A-like cells. The ghrelin-IR cells in the antrum were distinct from the gastrin cells, the serotonin-containing enterochromaffin cells and the D cells. Conceivably, ghrelin cells in the antrum and distally in the intestines also belong to the A-like cell population. The concentration of ghrelin in the circulation was lowered by about 80% following the surgical removal of the acid-producing part of the stomach in line with the view that the oxyntic mucosa is the major source of ghrelin. The serum ghrelin concentration was higher in fasted rats than in fed rats; it was reduced upon re-feeding and seemed unaffected by 1-week treatment with the proton pump inhibitor omeprazole, resulting in elevated serum gastrin concentration. Infusion of gastrin-17 for 2 days failed to raise the serum ghrelin concentration. Omeprazole treatment for 10 weeks raised the level of HDC mRNA but not that of ghrelin mRNA or somatostatin mRNA in the oxyntic mucosa. Hence, unlike the ECL cells, ghrelin-containing A-like cells do not seem to operate under gastrin control.

Mobilization of rat stomach ECL-cell histamine in response to short- or long-term treatment with omeprazole and/or YF 476 studied by gastric submucosal microdialysis in conscious rats.

1. Mobilization of histamine from the ECL cells was monitored by gastric submucosal microdialysis in conscious rats. The ECL cells are known to operate under gastrin control and the purpose of the present study was to examine their in situ response to short-term (12 h) as well as long-term (28 days) hypergastrinaemia, induced by treatment with the proton pump inhibitor omeprazole. 2. Hypergastrinaemia promptly raised the histamine concentration in the microdialysate. The effect was prevented by CCK(2) receptor blockade (YF476). On day 7 of omeprazole treatment the microdialysate histamine concentration reached a peak, five times higher than before treatment. Subsequently (14 and 28 days), less histamine was mobilized. 3. Gastrin infusion (4 h) raised the microdialysate histamine concentration in a dose-dependent manner in fasted rats and freely fed rats and in rats treated with omeprazole for a week. However, while fasted and fed rats responded to low doses of gastrin, the omeprazole-treated rats required large doses of gastrin to respond. 4. When the amount of histamine mobilized was related to the serum gastrin concentration the following EC(50) values could be calculated: fasted rats 2.3 x 10(-10) M, freely fed rats 2.5 x 10(-10) M, omeprazole-treated rats 8.7 x 10(-10) M. The maximal histamine responses in the three groups were 18.4 pmol 4 h(-1)+/-0.8, 21.9 pmol 4 h(-1)+/-1.2 and 68.0 pmol 4 h(-1)+/-3.5, respectively. 5. The results suggest that ECL cells, exposed to a high gastrin concentration for a week, respond with a shift in the receptor-ligand binding affinity from high to low. Apparently, CCK(2) receptors of the ECL cells are subject to dynamic changes with respect to ligand-binding affinity.