Gallbladder Contraction Research Articles

Comparison of fibroblast growth factor 19 concentrations between dogs with and without gallbladder mucoceles.

Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal-related flux of GB bile decreases serum FGF19 concentrations. Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty-two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. Prospective cross-sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8-67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5-285.1). In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Exogenous glucagon-like peptide 2 counteracts exogenous cholecystokinin-induced gallbladder contraction in healthy men.

Studies in humans and mice have demonstrated that the gut hormone glucagon-like peptide 2 (GLP-2) promotes gallbladder relaxation and refilling. Here, we assessed the effect of exogenous GLP-2 on gallbladder motility in the fasted state of healthy men with and without infusion of the potent gallbladder-contracting hormone cholecystokinin (CCK). In a randomized, double-blind, placebo-controlled, crossover study, 15 male participants (mean [SD]: age 24.7 [3.6] years; body mass index 22.9 [1.6] kg/m2) underwent four experimental days receiving two infusions on each day: either CCK (0.4 pmol × kg-1 × min-1, time 0-180 min) + GLP-2 (10 pmol × kg-1 × min-1, time 30-240 min), CCK + placebo, placebo + GLP-2, or placebo + placebo, respectively. Gallbladder volume was measured at baseline and throughout the 4-hour study day using ultrasonography. Compared to placebo + placebo, GLP-2 + placebo did not affect gallbladder volume, but when infused in combination with CCK, GLP-2 completely abolished the strong gallbladder-contracting effect seen during CCK + placebo infusion, restoring baseline levels of gallbladder volume. Exogenous GLP-2 counteracts exogenous CCK-induced gallbladder emptying in healthy men, pointing to a possible therapeutic potential for GLP-2 as a relaxing modulator of gallbladder smooth muscle tone (e.g., as bridge to surgery in biliary colic). The effect may also explain the gallbladder-related adverse events reported for GLP-2 receptor agonists used in the treatment of short bowel syndrome.

Oral SSTR5 Antagonist SCO-240 for Growth Hormone Stimulation: A Phase I Single-Dose Study in Healthy Individuals.

Somatostatin inhibits endocrine and exocrine secretion in various tissues by acting on five somatostatin receptor subtypes (SSTR1-5). The clinical effects of SSTR5 antagonism remain unknown. Herein, we evaluated the effects of SCO-240, an oral SSTR5 antagonist, in healthy individuals. This randomized, single-center, double-blind, placebo-controlled, phase I study included healthy Japanese and White individuals. The effects of ascending single oral doses of SCO-240 were evaluated in healthy individuals. The main outcome measures were safety, tolerability, pharmacokinetics, and pharmacodynamics (gallbladder contractions and levels of serum insulin and plasma glucagon-like peptide-1 (GLP-1)). The levels of pituitary hormones were evaluated in our exploratory analysis. The results indicated that SCO-240 was safe and well-tolerated at all tested doses. Oral SCO-240 was readily absorbed, with its systemic exposure increasing in a dose-dependent manner. The median time to maximum concentration and mean terminal half-life of SCO-240 were 3-4 and 10.2-12.6 hours, respectively, in the ascending dose section. No clinically meaningful changes in SCO-240 pharmacokinetic profiles were observed between fed and fasted or between Japanese and White individuals. No increase in gallbladder contractions or levels of insulin and GLP-1 were detected. SCO-240 induced robust growth hormone (GH) secretion without altering the levels of other pituitary hormones. In conclusion, the study is the first to demonstrate that SSTR5 antagonism stimulates GH secretion in humans. SCO-240 was safe and well-tolerated and exhibited once-daily oral dosing potential. The robust effects of SCO-240 on GH secretion suggest that it may be a treatment option for GH-related disorders.

Cholescintigraphic evaluation of gallbladder contraction in correlation with serum thyrotropin and serum cholesterol

Background and aims: To study the effect of serum thyrotropin (Sr.TSH) and serum cholesterol on gallbladder contraction by cholescintigraphy. Methods: This is a prospective cross-sectional study comprising 77 patients for evaluation of gallbladder function in patients with biliary pain. All of them underwent 99mTc- Mebrofenin fatty meal cholescintigraphy following a standard institutional protocol apart from regular investigations. Dynamic images were acquired for 90 minutes with a standardised fatty meal given at the 60th minute. Gallbladder emptying kinetics was determined with Gallbladder Ejection Fraction (GBEF) calculated at 30 minutes post-meal. Relevant statistical methods were applied for interpretation. Results: The mean of GBEF was 60.82% ± 16.65% and the mean of Sr.TSH was 3.72 ± 3.88 mIU/ml, there was a negative correlation between GBEF and Sr.TSH (Pearson correlation coefficient r = -0.535, p < 0.05). The mean serum cholesterol was 180.61 ± 46.34 mg/dl, there was a negative correlation between GBEF and serum cholesterol (Pearson’s correlation coefficient r = -0.685, p < 0.05). The mean GBEF in euthyroid and hypothyroid patients were 65.04% ± 15.04% and 47.27% ± 15.93% respectively (P < 0.05). Conclusion: Hypothyroidism is one of the key factors affecting gallbladder contractility and should not be overlooked in the management of functional gallbladder disorders. Cholescintigraphy can accurately assess gallbladder function qualitatively and quantitatively, and it can help (aid) physicians in diagnosing and decision-making on the management of biliary pain in hypothyroidism.

Discovery and exploration of novel somatostatin receptor subtype 5 (SSTR5) antagonists for the treatment of cholesterol gallstones

The shortage of cholesterol gallstones treatment intensifies the need to discover of effective small molecule drugs. Clinical follow-up and studies have found that activation of somatostatin receptor subtype 5 (SSTR5) reduce gallbladder contraction and thus increase the risk of cholesterol gallstones, implying that antagonizing SSTR5 may promote gallbladder emptying and reduce the formation of gallstones. Herein, we discovered novel SSTR5 antagonists and firstly investigated its effects on cholesterol gallstone. From loperamide, a reported seed structure with micromole activity, we identified optimal compound 23 as an SSTR5 antagonist exhibiting single-digit nanomolar potency, low hERG inhibition and oral availability. Further in vivo evaluation revealed that 23 significantly promoted gallbladder emptying. Moreover, in a mouse cholesterol gallstone model, 23 (3 mg/kg) effectively reduced the cholesterol gallstones formation, showing better efficacy than the clinical first-line drug UDCA (60 mg/kg), providing a new insight into the development of anti-gallstone drugs.

Ramadan intermittent fasting reduces visceral fat and improves gastrointestinal motility.

Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility. In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis. Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H2 peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn. RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.

Compounds Interacting with Cholecystokinin as Potential Drugs Against Excessive Weight Gain and Obesity

Cholecystokinin (CCK) is a peptide family that functions pancreatic enzyme secretion, gallbladder contraction, intestinal motility, satiety, and stomach acid secretion. The CCK peptides are derived from pro-CCK with a specific amino acid sequence (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) at their C-terminus, where the Tyr residue is sulfated. The CCK peptides are ligands of the CCK receptors 1 (CCK1) and 2 (CCK2). In this study, we propose an approach for treating overweight and obese patients, preventing or reducing CCK1 activation using compounds that specifically interact with CCK peptides to regulate their interactions with CCK1. The compounds were selected by molecular docking using a chemical library with the selected residues (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) in CCK. Their effects were evaluated in a diet-induced obese mice model. We show that compounds K2 and K5 decreased and maintained the body weight of the diet-induced obese mice model, respectively, likely by preventing/hindering interactions between CCK peptides and CCK1, modifying its activity. This study demonstrates another approach to treating overweight and obesity by regulating CCK1 functions. The K2 and K5 compounds have properties supporting their continued development as new drugs against these risk factors.

STUDY OF OCCURANCE OF GALL BLADDER STONES AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS IN A TERITIARY CARE HOSPITAL

Background: Diabetes could form cholesterol gallstones more frequently because of a reduced gallbladder contraction and increased biliary cholesterol secretion. A meta -analysis study suggested that there is a strong association between diabetes mellitus and the occurrence of gallstone disease. The incidence of gallstones is higher in Type 2 Diabetes both in males and females than the non-diabetics. To study the frequency of gallbladder stones among patients with Objective: Method: type 2 Diabetes mellitus. After institutional ethical committee approval and obtaining written informed consent from the patients, an observational cross-sectional study was conducted on patients admitted in Raja Rajeswari medical college and hospital over a period of one and half year on 100 known case of type II diabetes mellites for more than or equal to 5 years. In the present study, the Results: occurrence of gallbladder stones was 21% among Type 2 diabetes mellitus participants. Even though statistical association could not be proven, a higher HbA1c level was found to be among the study participants with gall stones when compared with the study participants without gall stones. 21% of the study participants were Conclusion: diagnosed with Gall stones. 79% of the study participants were not diagnosed with gall stones

Acute Cholecystitis from Biliary Lithiasis: Diagnosis, Management and Treatment

Biliary lithiasis is a global disorder affecting nearly 20% of the world's population, although most cases occur without symptoms. Gallbladder stones could move into the common bile duct after gallbladder contraction, causing acute cholecystitis. The progression of the acute disease can take different forms, from mild inflammation, treatable with oral antibiotics, to the most severe forms with septic shock or biliary peritonitis, requiring specific treatment. Liver function tests and abdominal ultrasound are generally sufficient for diagnostic purposes. The most commonly used antibiotic is penicillin, with piperacillin achieving the best results; alternatively, fluoroquinolones could also be used, although there is no univocal consensus and surgery remains the only definitive treatment. A prolonged antibiotic therapy after cholecystectomy seems inadvisable, except in severe cases and/or in the immuno-compromised patient, where it should be periodically evaluated to avoid antibiotic resistance and unnecessary use. This review presents an evidence-based analysis to describe the advantages and disadvantages of the available options for the treatment of biliary lithiasis and cholecystitis, from the pathophysiological mechanisms behind lithiasis formation and also covering the main diagnostic findings for biliary stones, recommending an approach tailored to the patient's characteristics and to the team's expertise.

Effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor in patients with gallstones.

Gallstones are a common digestive system disease. To assess the effects of laparoscopic and choledochoscopic gallbladder-preserving cholecystolithotomy on the levels of operation indicators, gallbladder function, and cholecystokinin type-A receptor (CCKAR) in patients with gallstones. The medical records of 100 patients with gallstones receiving operation from July 2019 to August 2022 were collected for retrospective analysis. They were divided into a laparoscopic group (n = 48) and a laparoscopic + choledochoscopic group (n = 52). The laparoscopic group received totally laparoscopic cholecystolithotomy, while the laparoscopic + choledochoscopic group underwent laparoscopic and choledochoscopic cholecystolithotomy. Their perioperative indicators, gallbladder function, stress indicators (cortisol (Cor), norepinephrine (NE), and C-reactive protein (CRP)), serum biochemical indicators (liver receptor homologue 1 (LRH-1), CCKAR, and vasoactive intestinal peptide (VIP)), and complications were compared. The fasting gallbladder volume and gallbladder contraction rate increased, and the minimum residual volume and gallbladder wall thickness decreased in the laparoscopic + choledochoscopic group in comparison with those of the laparoscopic group 6 months after operation (p < 0.05). The levels of serum Cor, NE, CRP, and CCKAR were elevated, whereas the levels of serum LRH-1 and VIP were lowered in both groups 3 d after operation compared with those before operation (p < 0.05). The levels of serum Cor, NE, CRP, LRH-1, and VIP were lower, and the level of serum CCKAR was higher in the laparoscopic + choledochoscopic group than those in the laparoscopic group 3 d after operation (p < 0.05). Both laparoscopic gallbladder-preserving cholecystolithotomy and laparoscopic and choledochoscopic cholecystolithotomy are effective for treating gallstones. However, the latter combination method is superior in enhancing postoperative gallbladder function, decreasing the recurrence risk, regulating the expressions of LRH-1, CCKAR, and VIP, and promoting the postoperative recovery of gastrointestinal function.

Relationship between gallstones and interstitial cells of Cajal in the gallbladder.

A high percentage of patients with gallstones exhibit abnormalities in gallbladder emptying, and gallstones are often associated with gallbladder contraction. Interstitial cells of Cajal (ICC) in the gallbladder are involved in the generation and spreading of spontaneous contractions of the gallbladder. This study examined the relationship among the number of gallbladder ICC, gallbladder contractility, and gallstones. Forty-six patients, who underwent cholecystectomy within 3 months of enduring a gallbladder ejection fraction scan, were enrolled in this study. ICC were identified using a microscope after immunohistochemical staining for CD117/c-kit. Five high-power field (magnification 400×) units were randomly assigned, and the number of ICC in the mucosal and muscular layers was counted. These counts were compared according to the sex, age, reason for cholecystectomy, presence of gallstone, presence of gallbladder polyp, gallbladder ejection fraction, and gallbladder size for each patient. The number of ICC in the mucosal layer was increased in the male participants (154.4 ± 73.9) compared with the female participants (107.3 ± 75.2); however, the ICC in the muscular layer was not different between the 2 groups. Additionally, the ICC in the mucosal and muscular layers did not differ according to age, cause of cholecystectomy, number of stones, stone character, stone diameter, or the presence of polyps. A larger gallbladder size was correlated with a decreased number of ICC in the muscular layer of the gallbladder. Additionally, when the number of gallbladder stones was increased, the number of ICC in the muscular layer of the gallbladder was decreased; however, there was no significant correlation between the number of ICC in the mucosal layer of the gallbladder and any of the following factors: age, GBEF, gallbladder size, stone number, or diameter. Furthermore, there was no significant correlation between the number of ICC in the muscular layer of the gallbladder, regardless of age, GBEF, and stone diameter. Although we were unable to achieve significant results regarding the relationship between GBEF and ICC, this is the first human study to reveal the relationship among ICC, gallbladder size, and the number of gallstones.

Molecular cloning of cholecystokinin (CCK) and CCK-A receptor and mechanism of CCK-induced gastrointestinal motility in Suncus murinus

Cholecystokinin (CCK) is a peptide hormone mainly secreted by small intestinal endocrine I-cells and functions as a regulator of gallbladder contraction, gastric emptying, gastrointestinal (GI) motility, and satiety. The cellular effects of CCK in these peripheral tissues are predominantly mediated via CCK-A receptors which are found in smooth muscles, enteric neurons, and vagal afferent neurons in humans and animal models. Although various functions of CCK have been reported to be neurally mediated, it can also stimulate contraction via the CCK receptor on the smooth muscle. However, the entire underlying neural and cellular mechanisms involved in CCK-induced GI contractions are not clearly understood. Here, we first determined the cDNA and amino acid sequences of CCK and CCK-A receptor along with the distributions of cck mRNA and CCK-producing cells in house musk shrew (Suncus murinus, the laboratory strain named as suncus) and examined the mechanism of CCK-induced contraction in the GI tract. Mature suncus CCK-8 was identical to other mammalian species tested here, and suncus CCK-A receptor presented high nucleotide and amino acid homology with that of human, dog, mouse, and rat, respectively. Suncus CCK mRNA and CCK-producing cells were found mainly in small intestine and colon. In the organ bath study, CCK-8 induced dose-dependent contractions in the suncus stomach, duodenum, and jejunum, and these contractions were inhibited by atropine and CCK-A receptor antagonist. These results suggest that CCK-8-induced contraction is mediated in the myenteric cholinergic neural network and that CCK-A receptor is partly responsible for CCK-8-induced contractions. This study indicates that suncus is a useful animal model to study the functions of CCK involved in GI motility.

The anatomy of the cystic duct and its association with cholelithiasis: MR cholangiopancreatographic study

The aims of this article are to detail the anatomy of the cystic duct in patients with and without gallstones as it relates to maneuvering of the duct during endoscopic transpapillary gallbladder cannulation, and to elucidate its role in the dynamics of bile flow during gallbladder contraction. One hundred MRCPs were retrieved from the prospectively maintained radiology data system to assess the configuration of the cystic duct and its confluence vis-a-vis the main biliary duct. The configuration of the cystic duct was broadly classified into four types: Angular (44%), Linear (40%), Spiral (11%), and Complex (5%). The level of emergence of the cystic duct from the bile duct was proximal in 29%, middle in 49% and distal in 20%. Its direction from the bile duct was to the right and angled upward in 69%, right and angled downward in 15%, left and angled upward in 13%, and left and angled downward in 1%. Its orifice was on the lateral surface of the bile duct in 50%, posterior in 19%, anterior in 15% and medial in 14%. In two cases, the cystic duct opened directly into the duodenum. Tortuous cystic ducts and non-lateral unions with the bile duct were significantly more prevalent in gallstone cases than the non-gallstone group (p=0.02). The present study details the spatial anatomy of the cystic duct vis a vis the main biliary duct. This has not been well investigated to date but has become increasingly relevant with the advent of recent gallbladder interventions.

Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters.

The gallbladder stores bile between meals and empties into the duodenum upon demand and is thereby exposed to the intestinal microbiome. This exposure raises the need for antimicrobial factors, among them, mucins produced by cholangiocytes, the dominant epithelial cell type in the gallbladder. The role of the much less frequent biliary tuft cells is still unknown. We here show that propionate, a major metabolite of intestinal bacteria, activates tuft cells via the short-chain free fatty acid receptor 2 and downstream signaling involving the cation channel transient receptor potential cation channel subfamily M member 5. This results in corelease of acetylcholine and cysteinyl leukotrienes from tuft cells and evokes synergistic paracrine effects upon the epithelium and the gallbladder smooth muscle, respectively. Acetylcholine triggers mucin release from cholangiocytes, an epithelial defense mechanism, through the muscarinic acetylcholine receptor M3. Cysteinyl leukotrienes cause gallbladder contraction through their cognate receptor CysLTR1, prompting emptying and closing. Our results establish gallbladder tuft cells as sensors of the microbial metabolite propionate, initiating dichotomous innate defense mechanisms through simultaneous release of acetylcholine and cysteinyl leukotrienes.

Systematic review and pathway enrichment analysis of Chinese medicine in preventing recurrence and improving prognosis of cholelithiasis after gallbladder-preserving lithotripsy.

Traditional Chinese medicine (TCM) may improve the prognosis management of cholelithiasis patients after gallbladder-preserving lithotripsy. To explore the evidence for this view, we systematically reviewed the efficacy and safety of TCM for improving the prognosis of cholelithiasis after gallbladder-preserving lithotripsy and performed functional pathway enrichment analysis of TCM target genes. In this systematic review (SRs), we searched six Chinese or international databases to collect randomized controlled clinical trials (RCTs) of TCM in preventing the recurrence of cholelithiasis after gallbladder-preserving lithotripsy. The literature was independently screened by 2 reviewers, who then extracted the data. The Cochrane risk-of-bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used to assess the included studies' risk of bias and quality of evidence, respectively. And, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses would be conducted on the TCM prescriptions in the included literature to find the effective component and mechanism of TCM in the prognosis management of gallbladder-preserving lithotripsy. Analysis in this research would be conducted by R 3.5.2 software. A total of 1,024 articles were retrieved, and 9 RCTs involving 926 participants were included after the step-by-step screening. The risk of bias for each important outcome in all the studies was "uncertain". The meta-analysis showed that compared with blank control, TCM prevented cholelithiasis by decreasing the recurrence rate, complications incidence, gallbladder wall thickness, and gallbladder contraction degree. But, there were no significant differences in the rate of the adverse reaction. The result of the GO and KEGG analysis revealed that the mechanism of prevention of TCM in gallstone recurrence may be related to the cholesterol metabolic pathway and that naringin from Glycyrrhiza may be the effective component in the prevention of recurrence. Existing evidence suggests that the use of TCM may reduce the recurrence rate after gallbladder-preserving lithotripsy and this effect may be related to the flavonoid glycoside naringin from Glycyrrhiza uralensis, but more RCTs with high quality in this area may be needed to have a robust conclusion.

Single versus multiple gall stone disease in patients undergoing laparoscopic cholecystectomy

The aim of this paper is to compare single versus multiple gall stone disease in patients undergoing laparoscopic cholecystectomy. A total of one hundred and thirty patients (males- 52, females- 78) within age group 20-65 years presented with cholelithiasis were divided into 2 groups. Group 1 comprised of single stone patients and group II had multiple stones. Each group had 65 patients. Parameters compared were symptoms and operative findings between both groups, Analysis of results was carried with chi0 square test. Most common clinical symptoms found to be fever in both groups (87%- group 1, 90%- group 2). Other symptoms were dyspepsia seen in 25% and 30%, nausea/ vomiting in 45% and 38% in group 1 and 2 patients respectively. Females were commonly affected and maximum case were observed in age group 40-50 years. Multiple gall stones patients had more symptoms and prevalence of conversion to open surgery was more in these patients. Group 1 patients showed gall bladder distention in 56 and group 2 in 62 patients, gall bladder contraction was seen in 6 patients in group 1 and 3 in group 2, adhesions were exhibited by 11 patients in group 1 and 20 in group 2. 4 patients in group 2 converted to open surgery. Gangrenous gall bladder was seen in 1 in group 1 and 5 in group 2.

51-Year-Old Man With Ascites and Abdominal Pain

51-Year-Old Man With Ascites and Abdominal Pain

Quantification of serum fibroblast growth factor-19 concentration in healthy dogs before and after feeding.

To measure serum fibroblast growth factor-19 (FGF-19) concentration and gallbladder volume in healthy dogs before and after feeding to determine whether serum FGF-19 concentration increases following gallbladder contraction and to assess FGF-19 stability in blood samples kept under different storage conditions after collection in tubes containing no anticoagulant or in serum separator tubes. 10 healthy dogs of various ages and breeds (30 blood samples and 30 gallbladder volume measurements). Serum FGF-19 concentration was measured with a commercially available ELISA. Gallbladder volume was determined ultrasonographically. Blood samples and gallbladder measurements were obtained from the dogs after food had been withheld for 12 hours (baseline) and at 1 and 3 hours after feeding. The stability of serum FGF-19 was assessed in samples collected in tubes containing no anticoagulant or in serum separator tubes and stored at -80°C for variable intervals or 4°C for 1 or 5 days. Serum FGF-19 concentration was significantly increased from baseline at 1 and 3 hours after feeding. There was a significant decrease in gallbladder volume 1 hour after feeding, compared with baseline findings. Regardless of collection tube used, concentrations of FGF-19 in serum obtained from blood samples that were collected and immediately stored at -80°C differed significantly from concentrations in serum obtained from blood samples that had been collected and stored at 4°C for 5 days. Results indicated that postprandial gallbladder contraction results in increases of serum FGF-19 concentration in healthy dogs. Assessment of circulating FGF-19 concentration could be used to detect disruptions in the enterohepatic-biliary axis in dogs.

A Comparison of Gallbladder Contraction Index in Diabetics and Non diabetics using Ultrasonogram: A Cross-sectional Study

A Comparison of Gallbladder Contraction Index in Diabetics and Non diabetics using Ultrasonogram: A Cross-sectional Study

1215-P: Effects of Exogenous Secretin on Postprandial Plasma Glucose and Lipids and Gallbladder Motility and Hemodynamics in Man

Secretin is best known for its effect on pancreatic exocrine secretion. It also has osmoregulatory effects and was recently identified as a potential target for the treatment of obesity. We investigated the effects of a 5-hour intravenous (iv) secretin infusion on postprandial plasma glucose and lipids and gallbladder motility as well as hemodynamics in healthy males. In a randomized, double-blind, placebo-controlled, crossover study, 25 healthy males (25.7 ± 6.1 (mean ± SD) years; BMI 23.4 ± 1.8 kg/m2) underwent two 5-hour iv infusions of secretin (1 pmol/kg/min) or placebo (saline), with an interposed 8-week washout period. After 30 minutes of infusion, a standardized liquid mixed meal was ingested. Prior to and with regular intervals during the 5-hour infusions, blood samples were drawn, ultrasonography of the gallbladder performed, and hemodynamics measured. Steady-state plasma concentrations of secretin amounted to 113 ± 2 pmol/L, i.e., ~20-fold higher than physiological levels. Postprandial plasma triglyceride excursions were higher during secretin than placebo infusions (baseline-subtracted area under curve: 111 ± 49 vs. 83 ± 36 min × pmol/L [P = 0.012]), whereas excursions in glucose, glycerol and free fatty acids were similar during placebo and secretin infusions. Compared to placebo, secretin reduced maximum gallbladder ejection fraction by 32 ± 27% (P &amp;lt;0.001) and increased mean systolic and diastolic blood pressure by 5.3 ± 4.5 (P &amp;lt;0.039) and 2.2 ± 3.2 mmHg (P &amp;lt;0.001), respectively, and increased heart rate by 5.5 ± 3.6 bpm (P &amp;lt;0.001). We conclude that a 5-hour iv infusion of secretin in healthy males has no effect on fasting and postprandial glucose levels, but reduces postprandial gallbladder contraction, while increasing plasma triglycerides, blood pressure and pulse. Disclosure M. J. Bentzen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. M. B. Christensen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.