Plasma Gastrin Levels Research Articles

Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism

BackgroundAmong bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide. MethodsIn 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured. ResultsSG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group. ConclusionGastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

Effects of Modified Baizhu Shaoyao San on Postoperative Diarrhea in Colorectal Cancer Patients: A Single-Blind, Randomized Controlled Trial

Introduction: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients. Methods: Eighty patients with colorectal cancer were randomized within 2 weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA. Results: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the TCM syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased. Conclusion: The curative effect and safety of modified BSS were statistically significant.

Proton Pump Inhibitors and Cancer: Current State of Play.

Background: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are overprescribed in patients with cancer; there is increasing evidence of their effects on cancer development and survival. The objective of this narrative review is to comprehensively identify cancer medications that have clinically meaningful drug–drug interactions (DDIs) with PPIs, including loss of efficacy or adverse effects, and to explore the association between PPIs and cancer. Methods: A PubMed search of English language studies published from 1 January 2016, to 1 June 2021 was conducted. The search terms included “proton pump inhibitors,” “cancer,” “chemotherapy,” “immunotherapy,” “hormonotherapies,” “targeted therapies,” “tyrosine kinase inhibitors,” and “gut microbiome”. Recent and relevant clinical trials, meta-analyses, and reviews were included. Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their impact on cancer survival remains unclear. PPIs may decrease the efficacy of some antineoplastic agents through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate). More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome. PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies but may have a protective effect on the renal system. Discussion/Conclusions: PPIs may interact with the cancer microbiome and the efficacy of various antineoplastic agents, although only a few DDIs involving PPIs are clinically significant. Further pharmaco-epidemiological studies are warranted, but physicians should be aware of the potential consequences of PPI use, which should be dose appropriate and prescribed according to guidelines.

Impacts of Betaine Addition in Sow and Piglet's Diets on Growth Performance, Plasma Hormone, and Lipid Metabolism of Bama Mini-Pigs.

The present study evaluated the effects of betaine addition in sow and piglet's diets on growth performance, plasma hormone, and lipid metabolism of Bama mini-pigs. A total of 26 pregnant Bama mini-pigs and 104 weaned piglets were selected and divided into different dietary treatment groups (details in “Materials and Methods”). Blood and muscle samples were collected at 65-, 95-, and 125-day-old, respectively. The results showed that betaine addition in sow-offspring diets increased (P < 0.05) the body weight at 125-day-old, average daily gain from 35- to 65-day-old, and average daily feed intake at 35–65 and 35–95 days old of pigs compared with the control group. Betaine addition in sow-offspring diets increased (P < 0.05) the plasma gastrin level at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the plasma peptide YY and leptin levels at 65-day-old pigs. In the longissimus dorsi muscle of pigs, betaine addition in sow and sow-offspring diets increased (P < 0.05) the C12:0 content at 65-day-old while decreased at 95-day-old. Moreover, betaine addition in sow-offspring diets increased the C24:0 content and decreased the C18:1n9t content at 125-day-old (P < 0.05). In the biceps femoris muscle, the contents of C12:0 at 65-day-old and C20:4n6 at 125-day-old were decreased (P < 0.05) after the betaine addition in both sow and piglet's diets. In addition, betaine addition in sow diets decreased (P < 0.05) the C20:0 content at 125-day-old, while betaine addition in sow-offspring diets increased the C18:3n6 and decreased C24:0 contents at 65-day-old pigs (P < 0.05). In the psoas major muscle, betaine addition in sow and sow-offspring diets decreased (P < 0.05) the contents of C18:1n9t at 65-day-old and C20:1 at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the intramuscular fat content at 125-day-old. Moreover, betaine addition in sow-offspring diets was also associated with muscle lipid deposition and metabolisms by regulating the gene expressions related to fatty acid metabolism. These findings suggested that betaine addition in sow-offspring diets could improve the growth performance, whereas betaine addition in both sow and sow-offspring diets could enhance lipid quality by altering plasma hormone level and fatty acid composition and regulating the gene expressions related to fatty acid metabolism.

Changes of Gastric Secretion after Bolus and Slow Intravenous Administration of Bombesin and Neurotensin

Objectives:The aim of the present study was to evaluate the changes caused by intravenous administration of regulatory peptides, bombesin (BBS) and neurotensin (NT), on gastric secretion, serum gastrin, and plasma levels of bombesin-1ike immunoreactivity (BLI) and neurotensin. Materials and methods: Fourteen dogs underwent an upper gastrointestinal tract operation and a Pavlov pouch for the concentration of gastric fluids was formed. The experimental animals were divided into two groups. Peptides were given one month after the second operation and after fasting for 12 hours. In group A, the effects of BBS were studied after a rapid 1 ìg/kg body weight dose and a slow 30´ 0.5 ìg/kg body weight dose administration intravenously. Correspondingly to group B the effects of NT were studied in the same way. Results:The rapid intravenous infusion of BBS caused a very significant increase in gastrin levels, BLI in plasma, volume and HCl of the gastric fluids. The same results, plus a significant decrease in gastric pH, were observed following slow intravenous infusion of BBS. Concerning the NT, rapid administration caused a significant decrease in the volume of gastric fluids. Slow NT administration of caused a significant reduction in gastric fluid volume and in HCl. On the contrary, pH was significantly increased. Conclusion:Bombesin increases plasma gastrin levels and HCl secretion. Neurotensin administration causes a decrease in HCl secretion without affecting gastrin levels in plasma.

Efficacy of Nx4 to Reduce Plasma Cortisol and Gastrin Levels in Norwegian Sled Dogs During an Exercise Induced Stress Response: A Prospective, Randomized, Double Blinded, Placebo-Controlled Cohort Study.

Introduction: An exercise induced stress response is commonly seen in high performance sled dogs, resulting in increased plasma cortisol. A stress induced rise of cortisol might result in increased prevalence of gastritis and gastric ulcers mediated by an increase of gastrin. Neurexan® (Nx4) is a medicinal product used for stress relief by reduction of cortisol. The aim of the study was to show that Nx4 reduces plasma cortisol and plasma gastrin in high performance sled dogs and to show tolerability of Nx4 in dogs.Material and Methods: First, a pilot study was done to validate the increase of cortisol by performance. The data from the pilot study was used for sample size estimation via an adapted power analysis as well as the identification of important variables. These were then used in the randomization procedure of the main study. Second, a prospective randomized, double blinded, placebo-controlled cohort study was conducted. The main study included 45 sled dogs, assigning 23 dogs to the Nx4 group, and 22 dogs to the placebo group, to analyze plasma cortisol and plasma gastrin at four time points: before, directly after and 30 and 120 min after performance.Results: For the main target variable, area under the curve (AUC) of plasma cortisol, a significantly lower adjusted mean value in the Nx4 group compared to the placebo group (p = 0.031) was found. Plasma gastrin was also significantly reduced in the Nx4 group 30 min after performance (p = 0.023), resulting in a significantly reduced plasma gastrin AUC in the Nx4 group compared to the placebo group (p = 0.049).Discussion: Within the limitation of the study, the results carry implications for the usefulness of Nx4 to reduce exercise induced plasma cortisol and gastrin levels. The reduction of the exercise induced stress response could help to improve the welfare of high-performance sled dogs. Since activation of the hypothalamic-pituitary-adrenal axis resulting in increased cortisol is similar for exercise induced stress and psychologic stress, the same might be true independent of the stressor, making Nx4 potentially useful in any stressful situation for dogs.

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.

Gastrin and the Moderate Hypergastrinemias.

The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to Helicobacter pylori infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.

Effects of First Feed Administration on Small Intestinal Development and Plasma Hormones in Broiler Chicks.

Simple SummaryIn this study, the effects of first feed administration on intestinal morphology, barrier function, and plasma hormones in broilers during the initial 168 h posthatch. Results revealed that early feeding posthatch had a positive effect on small intestinal growth by increasing weight and improving intestinal morphology and barrier function. In other words, early feeding promoted intestinal development, which could be very meaningful for commercial broiler production.(1) Background: Under practical conditions, newly hatched chicks were usually withheld feed and water for 48 to 72 h. It was shown that early feeding after hatch promoted gastrointestinal development of broiler chicks. However, the mechanism of early feeding affecting intestinal development in chicks needs further research. The present study was conducted to investigate the effects of first feed administration on intestinal morphology, barrier function, and plasma hormones in broilers during the initial 168 h posthatch. (2) Methods: A total of 720 one-day-old chicks (newborn chick, Lingnan Yellow) were placed 2 h after hatch and randomly assigned to three treatments: Group A (feed immediately after placement), Group B (fasting for 24 h after placement), and Group C (fasting for 48 h after placement). The trial lasted for 168 h and water ad libitum all the time. Sampling was performed at 0, 24, 48, 72, 120, and 168 h. (3) Results: Higher (p < 0.05) absolute weight and relative weight of the small intestine were observed in Group A. Moreover, the villus height, crypt depth, and ratio of the jejunum and ileum were significantly higher (p < 0.05) in Groups A and B than those in Group C. Microvilli of the duodenum were closely packed in Group A but sparse and disorganized in Groups B and C. The expression levels of mRNA and protein of tight junction genes (occludin and claudin-1) were upregulated (p < 0.05) in Group A. The levels of gastrin and insulin in plasma were decreased (p < 0.05) significantly in the Groups B and C. However, chicks in Groups B and C had higher (p < 0.05) plasma glucagon levels at 24 and 48 h after placement. (4) Conclusions: These results suggested that early feeding posthatch had a positive effect on small intestinal growth increasing weight and improving intestinal morphology and barrier function.

Bypassed and Preserved Stomach Resulted in Superior Glucose Control in Sprague-Dawley Rats with Streptozotocin-Induced Diabetes

Recent studies suggest the possibility of the stomach playing a role in diabetes remission after bariatric surgery. In this study, we investigated whether bypassing the stomach alleviates diabetes in diabetic rodent model. Eighteen moderately obese and diabetic Sprague-Dawley rats were randomly assigned to Esophagoduodenostomy with or without gastric preservation (EDG and EDNG/total gastrectomy, respectively), and SHAM groups. Bodyweight, food intake, fasting glucose level, oral glucose tolerance test result (OGTT), and hormone levels (insulin, glucagon-like peptide-1, ghrelin, gastrin and glucagon) were measured preoperative and postoperatively. Postoperatively, bodyweight and food intake did not differ significantly between the EDG and EDNG groups. Postoperative fasting blood glucose and OGTT results declined significantly in the EDG and EDNG group when compared with the respective preoperative levels. Postoperative glucose control improvements in EDNG group was significantly inferior when compared to EDG. Compared preoperatively, postoperative plasma ghrelin and gastrin levels declined significantly in EDNG group. Preoperative and postoperative plasma GLP-1 level did not differ significantly among all the groups. Postoperatively, EDG group had significantly higher insulin and lower glucagon levels when compared with SHAM. In conclusion, bypassing and preserving the stomach resulted in superior glucose control improvements than total gastrectomy.

Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.

Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. We evaluated 220 children and adolescents (11.28 ± 6.37years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18years were invited to undergo a gastroscopic exam. PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7years of follow-up in AT and 4.4 ± 4.0years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux

Background/Aim: We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE). Methods: Despite ≥8 weeks of appropriate PPI therapy, patients with ­persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed. Results: From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved. Conclusion: In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

Gastrin, Histamine Prostaglandin: Indicators for assessing efficacy of cimetidine, Omeprazole and Ranitidine in Gastric Ulcer Treatment

Background and Objectives: There is increase prevalence of gastric ulcer in the society, but the drugs that are sensitive for radical cure are not screened with physiologic markers such which affect proper management of the disease. The objective of the study is to relate various sources or organ specific templates: gastrin, histamine and prostaglandin relating with the disease in evaluating the potencies of cimetidine, ranitidine and omeprazole for best choice of the drugs in gastric ulcer disease treatment.Material and Methods: Plasma, gastric and antral prostaglandins, histamine and gastrin levels were studied in ninety-six (96), male and female Swiss albino rats for 28 days, using high performance liquid chromatography.Results: Male and female rats with gastric ulcer treated with cimetidine, omepraszole and ranitidine showed no significant difference (P&gt;0.5) in gastrin and the drug groups in plasma, gastric and antral concentrations. But, there was significant difference (P&lt;0.05) in histamine levels between cimetidine, omeprazole and ranitidine in their gastric and plasma concentration. There was no significant difference (P&gt;0.05) in prostaglandin values between cimetidine, omeprazole and ranitidine. Also there was no significant difference (P&gt;0.05) in gastric and plasma levels of gastrin, histamine and prostaglandin between 7, 14, 21 and 28 days treatment period. But, there was significant difference (P&lt;0.05) in antral concentration of gastrin, histamines and prostaglandin between the drug groups. However, there was no significant difference (P&gt;0.05) in antral gastrin between male and female rats in cimetidine and ranitidine treatment. The three drugs were associated with high levels of gastrin, histamine, low prostaglandin though cimetidine showed higher concentration of prostaglandin.Conclusion: It is concluded that gastrin, histamine and prostaglandin are sensitive indicators in evaluating anti-ulcerogenic drugs efficacies.Janaki Medical College Journal of Medical Sciences (2017) Vol. 5(2): 5-12

Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions

BackgroundCurcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied. We determined the effect of curcumin against gastric haemorrhagic lesions induced by 75% ethanol and alterations in gastric blood flow (GBF) in rats with cyclooxygenase-1 (COX-1) and COX-2 activity inhibited by indomethacin, SC-560 or rofecoxib, inhibited NO-synthase activity, capsaicin denervation and blockade of TRPV1 receptors by capsazepine.MethodsOne hour after ethanol administration, the gastric mucosal lesions were assessed by planimetry, the GBF was examined by H2 gas clearance, plasma gastrin was determined by radioimmunoassay, and the gastric mucosal mRNA expression of Cdx-2, HIF-1α, HO-1 and SOD 2 was analysed by RT-PCR.ResultsCurcumin, in a dose-dependent manner, reduced ethanol-induced gastric lesions and significantly increased GBF and plasma gastrin levels. Curcumin-induced protection was completely reversed by indomethacin and SC-560, and significantly attenuated by rofecoxib, L-NNA, capsaicin denervation and capsazepine. Curcumin downregulated Cdx-2 and Hif-1α mRNA expression and upregulated HO-1 and SOD 2, and these effects were reversed by L-NNA and further restored by co-treatment of L-NNA with l-arginine.ConclusionsCurcumin-induced protection against ethanol damage involves endogenous PG, NO, gastrin and CGRP released from sensory nerves due to activation of the vanilloid TRPV1 receptor. This protective effect can be attributed to the inhibition of HIF-1α and Cdx-2 expression and the activation of HO-1 and SOD 2 expression.

Adrenalectomy abolishes hypergravity-induced gastric acid hyposecretion.

Jet fighter pilots experience high gravitational acceleration forces in the cephalocaudal direction (+Gz), causing severe stress. Stress affects different physiological functions of the gastrointestinal tract. Although the effects of exposure to hypergravity on cardiovascular and cerebral functions have been the subject of numerous studies, crucial information regarding potential pathophysiological alterations following hypergravity exposure in the gastrointestinal tract is lacking. We recently documented a significant decrease in gastric secretory activity in rats after acute exposure to hypergravity. In the present study, we investigated the effects of adrenalectomy on gastric acid secretion and plasma gastrin level in hypergravity-exposed rats. Male Sprague-Dawley rats were adrenalectomized and exposed to +10Gz three times for 3 min. Gastric juice and blood samples were collected, and the volume and total acidity of gastric juice and plasma level of gastrin were measured. Consistent with our previous data, acute exposure to +10Gz significantly altered the gastric juice parameters in the sham-operated rats. The volume (P < 0.001) and acidity (P < 0.001) of gastric juice in the hypergravity-exposed rats were significantly lower than those in the nonexposed rats. In contrast, in adrenalectomized rats, the differences in the gastric juice volume (P = 0.712) and acidity (P = 0.279) were not statistically significant between the hypergravity-exposed and nonexposed rats. We demonstrated that adrenalectomy abolished hypergravity-induced gastric acid hyposecretion, but did not influence gastrin release. These findings suggest that the adrenal glands are required for hypergravity-induced gastric acid hyposecretion.

Enterohormonal disturbances in colorectal cancer patients.

Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

Gastric acid response to acute exposure to hypergravity.

The influence of environmental stressors on the pathogenesis of gastrointestinal disease has received increased awareness. Stress affects different physiological functions of the gastrointestinal tract, including gastric acid secretion and mucosal blood flow. Repeated exposures of rapid-onset, highly-sustained hypergravity cause severe physical stress in the pilot. Although the effects of exposure to hypergravity on cardiovascular and cerebral functions have been the subjects of numerous studies, crucial information regarding pathophysiological changes in the gastrointestinal tract following hypergravity exposure is lacking. In this study, we investigated the effects of acute exposure to hypergravity on gastric secretory activity and gastrin release. Male Sprague-Dawley rats were exposed to +10Gz three times for 3 min. Gastric juice and blood were collected. The volume and total acidity of gastric juice, and the plasma gastrin level was measured. Acute exposure to +10Gz significantly decreased the gastric juice parameters. The gastric juice volume and total acidity of hypergravity-exposed rats were 3.54 ± 0.32 mL/100 g and 84.90 ± 5.17 mEq/L, respectively, which were significantly lower than those of the nonexposed rats (4.62 ± 0.39 mL/100 g and 97.37 ± 5.42 mEq/L; P < 0.001 and P < 0.001, respectively). In contrast, plasma gastrin level was not significantly altered following hypergravity exposure. We demonstrated that acute exposure to hypergravity led to a significant decrease in the gastric juice volume and acidity but did not alter the plasma gastrin level.

Gastrorenal Axis.

Gastrorenal Axis.

Effect of combined Metformin and Esomeprazole therapy on plasma gastrin and blood glucose in elderly patients with type 2 diabetes mellitus

Objective To investigate the effect of combined Metformin and esomeprazole therapy on plasma levels of gastrin, blood glucose, glycosylated hemoglobin(HbA1c)and insulin in elderly patients with type 2 diabetes. Methods A randomized, double-blind, placebo-controlled study of 41 elderly patients with type 2 diabetes was conducted.Patients were randomly assigned into treatment group(combination therapy with Metformin 0.5 g, bid or tid and Esomeprazole 20 mg, qd, for 12 weeks)and placebo group(Metformin monotherapy 0.5 g, bid or tid, for 12 weeks). Fasting blood samples were taken from vein before and after treatment.Fasting serum levels of gastrin, glucose, HbA1c, insulin, lipids, liver and renal functions were compared between the two groups.The homeostasis model of assessment for insulin resistance index(HOMA-IR)and insulin secretion index(HOMA-β)were calculated, and complications were recorded. Results There were no significant differences in body mass index and waist circumference between the two groups.Serum gastrin level was slightly increased in the treatment group 12 weeks after treatment, but without statistically significance 〔(127.20±9.21)ng/L vs.(131.53±7.84)ng/L, P>0.05〕, and serum gastrin level had no significant differences in the placebo group before and after treatment 〔(128.42±4.58)ng/L vs.(127.51±3.47)ng/L, P>0.05〕. However, there were no significant differences in the changes of blood glucose, HbA1c, insulin, HOMA-β and HOMA-IR before versus after therapy, and between the two group(all P>0.05). Conclusions Combined Metformin and insulin therapy cannot increase serum gastrin and insulin levels and has no significant effect on reducing blood glucose and HbA1c levels in elderly patients with type 2 diabetes. Key words: Diabetes mellitus, type 2; Proton pump inhibitor; Metformin; Gastrins; Blood glucose

Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control.

Experimental data demonstrated that gastrin has incretin-like stimulating actions on β-cells, resulting in a promotion of glucose-induced insulin secretion. As proton pump inhibitors (PPIs) consistently increase plasma gastrin levels, a possible effect of this treatment on glucose-insulin homeostasis may be hypothesized. Therefore, the aim of this study was to evaluate the effect of chronic PPIs treatment on glycemic control in patients affected by type 2 diabetes. This is an observational, retrospective study. A total of 548 consecutive patients with type 2 diabetes (mean age ± SD: 67.1 ± 10.9 years, M/F: 309/239, diabetes duration: 12.4 ± 9.8 years) referring to our diabetes outpatient clinics were enrolled; among them, 45 %were treated with PPIs longer than 2 years for preventive/therapeutic purposes. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), serum lipids and transaminases were measured by standard laboratory methods. Major cardiovascular events and concomitant medications were recorded in all participants, and daily insulin requirement was calculated in insulin-treated subjects. PPIs-treated patients had significantly lower HbA1c (7.1 ± 1.07 %-54.1 ± 12 vs 7.4 ± 1.4 %-57.4 ± 8 mmol/mol, p = 0.011) and FPG (127 ± 36.9 vs 147.6 ± 49.4 mg/dl, p < 0.001) levels than those untreated. These differences increased in patients under insulin therapy and in those with concomitant PPIs + GLP-1-based therapy. The multivariate regression analysis demonstrated that the association between chronic PPIs treatment and HbA1c was independent from possible confounders (p = 0.01). PPIs treatment is associated with greater glycemic control in patients with type 2 diabetes, particularly in those on insulin- or GLP-1-based therapy. Our results suggest a role for PPIs in glucose-insulin homeostasis and may open a new scenario for diabetes therapy.