Sphincterotomy for biliary sphincter of Oddi dysfunction.

The review is withdrawn as it has not been maintained since its first publication in 2001 (searches date back to the year 2000). Since then, new trials have been published that may or may not change the conclusions of the review. A new team of authors overtook the review on 26.10.2020, and the new review is expected to be published by the beginning of 2022. The review will be prepared based on most recent Cochrane methods. Readers may still find the outdated review on the CDSR (the Cochrane Library).

Influence of Asian Ethnicities on Short- and Mid-term Outcomes Following Laparoscopic Sleeve Gastrectomy.

PURPOSE: Prevalence of obesity in Asia has been on the increasing trend, with corresponding increase in utilisation of bariatric surgery. The objective of this study was to examine differences in weight loss outcomes following bariatric surgery between Asian ethnicities. MATERIALS AND METHODS: A retrospective database review was conducted of patients undergoing primary laparoscopic sleeve gastrectomy between 2009 and 2013 in 14 centres from Singapore, Malaysia, Taiwan, Hong Kong, Japan, Korea, India, Australia, Switzerland, and the USA. All patients with available follow-up data at 12 months and 36 months post-surgery were included in this study. Outcome measures used were percentage excess weight loss (%EWL) and percentage total weight loss (%TWL). Differences in outcomes between ethnicities were analysed after adjusting for age, gender, baseline body mass index (BMI), and presence of diabetes. RESULTS: The study population (n = 2150) consisted of 1122 Chinese, 187 Malays, 309 Indians, 67 Japanese, 259 Koreans, and 206 Caucasians. 67.1% were female and 32.9% were male. Mean age was 37.1 ± 11.2 years. Mean pre-operative BMI was 40.7 ± 8.1 kg/m2. With the Caucasian population as reference, Japanese had the best %TWL (3.90, 95% CI 1.16-6.63, p < 0.05) and %EWL (18.55, 95% CI 10.33-26.77, p < 0.05) while the Malays had the worst outcomes. Both Chinese and Koreans had better %EWL but worse %TWL as compared to Caucasians and there were no significant differences with the Indian study group. CONCLUSION: There are differences in weight loss outcomes following bariatric surgery between Asian ethnicities.

Intermittent Vagal Nerve Block for Improvements in Obesity, Cardiovascular Risk Factors, and Glycemic Control in Patients with Type 2 Diabetes Mellitus: 2-Year Results of the VBLOC DM2 Study.

BACKGROUND: One-year results of the VBLOC DM2 study found that intermittent vagal blocking (VBLOC therapy) was safe among subjects with obesity and type 2 diabetes mellitus (T2DM) and led to significant weight loss and improvements in glycemic parameters and cardiovascular risk factors. Longer-term data are needed to determine whether the results are sustained. METHODS: VBLOC DM2 is a prospective, observational study of 28 subjects with T2DM and body mass index (BMI) between 30 and 40 kg/m(2) to assess mid-term safety and weight loss and improvements in glycemic parameters, and other cardiovascular risk factors with VBLOC therapy. Continuous outcome variables are reported using mixed models. RESULTS: At 24 months, the mean percentage of excess weight loss was 22% (95% CI, 15 to 28, p < 0.0001) or 7.0% total body weight loss (95% CI, 5.0 to 9.0, p < 0.0001). Hemoglobin A1c decreased by 0.6 percentage points (95% CI, 0.2 to 1.0, p = 0.0026) on average from 7.8% at baseline. Fasting plasma glucose declined by 15 mg/dL (95% CI, 0 to 29, p = 0.0564) on average from 151 mg/dL at baseline. Among subjects who were hypertensive at baseline, systolic blood pressure declined 10 mmHg (95% CI, 2 to 19, p = 0.02), diastolic blood pressure declined by 6 mmHg (95% CI, 0 to 12, p = 0.0423), and mean arterial pressure declined 7 mmHg (95% CI, 2 to 13, p = 0.014). Waist circumference was significantly reduced by 7 cm (95% CI, 4 to 10, p < 0.0001) from a baseline of 120 cm. The most common adverse events were mild or moderate heartburn, implant site pain, and constipation. CONCLUSIONS: Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

Effect of a post-operative structured exercise programme on short-term weight loss after obesity surgery using adjustable gastric bands.

BACKGROUND: Exercise has been recommended as an adjunct to diet control to achieve weight loss. No previous studies in the area had formal exercise guidelines or education [1, 2]. Unique to our practice is Bandfit, a personal trainer-led exercise programme for patients following bariatric surgery. METHODS: We analysed the effect of Bandfit on short-term weight loss. A retrospective review of a prospectively collected database of consecutive patients between 2007 and 2008 was undertaken. Patients were educated about appropriate exercises for obese people with active participation. Percentage excess weight loss was calculated at 12 and 36 months. Weights were accepted ±3 months following the gastric banding. Patients were divided into subgroups based on zero, one or greater than one session attended. Patients without available records, 12-month data or a rural address were excluded. Data were statistically analysed utilising a two-sample t test and an analysis of variance (ANOVA) calculation. RESULTS: One hundred sixty-three patients were eligible for inclusion with 26 excluded as described in the methods. In the remaining 137 patients, 49 (36 %) did not attend any sessions, 28 (20 %) attended one, and 60 (44 %) attended more than one session. CONCLUSIONS: Analysis of the %EWL and sessions attended demonstrated a significant difference between those who attended more than one Bandfit session (p < 0.03), compared to those who did not attend any. However, this effect was not seen at 36 months. Attendance at a dedicated educational exercise programme significantly enhances short-term weight loss, but the effect is not seen at 36 months.

Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

IMPORTANCE: Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE: To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS: One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES: The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS: In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE: Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01327976.

The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.

BACKGROUND: Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia. METHODS: Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n = 192) or control (n = 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM. RESULTS: Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m(2), and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥ 12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively. CONCLUSIONS: VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Serologic predictors of nonalcoholic steatohepatitis in a population undergoing bariatric surgery.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common in the morbidly obese. It is a condition that can lead to progressive fibrosis and cirrhosis. We determined the prevalence in a population undergoing bariatric surgery and evaluated the possible serologic predictors before the development of fibrosis. METHODS: Liver biopsies were taken from 370 consecutive patients who were undergoing laparoscopic bariatric surgery. The clinical and biochemical parameters were then assessed for correlation with the histologic features of nonalcoholic steatohepatitis. RESULTS: Of the 370 patients, 68 (18%) were found to have NASH. Increased insulin resistance, alanine transaminase, and total bilirubin were independently associated with the presence of NASH. The presence of ≥ 2 of the 3 provided the best combination of sensitivity (.71) and specificity (.71) for predicting NASH. CONCLUSION: Increased insulin resistance, alanine transaminase, and total bilirubin are serologic predictors for the presence of NASH before the development of fibrosis.

Gastric band erosion in 63 cases: endoscopic removal and rebanding evaluated.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) remains the most popular bariatric procedure performed in Australia and Europe. Gastric band erosion is a significant complication that results in band removal. The aim of this study is to assess the prevalence of band erosion and its subsequent management with a particular focus on rebanding results. METHODS: Patients who underwent LAGB in a prospective cohort study from August 1996 to October 2010 were evaluated. Patients that developed band erosion were identified and clinical presentations, band characteristics and subsequent management were evaluated. RESULTS: One thousand eight hundred seventy-four morbidly obese patients underwent LAGB. Band erosion developed in 63 patients (3.4%). Median preoperative BMI was 41.5 kg/m(2) (range 30-61 kg/m(2)). Median time from operation to diagnosis was 39 months (range 6-132 months). Twenty nine patients (46%) were asymptomatic (sudden loss of restriction, weight gain, turbid fluid, or absence of fluid). Symptoms included abdominal pain in 24 (38%), obstruction in 7 (11%), recurrent port infection in 5 (8%), reflux symptoms in 2 (3%) and sepsis in 2 (3%). Fourteen patients (22%) had discolouration of the fluid in their band. Endoscopic removal was attempted in 50 patients with successful removal in 46 (92%). Median number of endoscopies prior to removal was 1.0 (range 1-5). The median duration of the procedure was 46 min (range 17-118 min). Rebanding was performed in 29 patients and 5 (17%) experienced a second erosion. Mean percentage excess weight loss was 54% in the remaining 22 patients with at least 3 months follow-up. CONCLUSIONS: Band erosion prevalence was 3.4%. Endoscopic removal of eroded gastric bands was proven safe and effective. Band erosion is now preferably managed endoscopically in our institution. Rebanding following erosion results in acceptable weight loss but an unacceptable reerosion rate.

Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice.

BACKGROUND: We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP. METHODS: Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured. RESULTS: Galantide significantly reduced AP-induced hyperenzymaemia by 39-45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28-45%. CONCLUSIONS: Treatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion.

BACKGROUND: Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS: A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS: Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin

The islet-acinar axis of the pancreas: more than just insulin.

Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding. The interrelationship between the endocrine and exocrine pancreas is mediated by islet-derived hormones such as insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and also neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) released by the nerves innervating the pancreas. Although considerable progress has been achieved, further work is required to fully delineate the complex interplay of the numerous mechanisms involved. This review aims to provide a comprehensive update of the current literature available, bringing together data gleaned from studies addressing the actions of individual hormones, humoral factors, and neurotransmitters on the regulation of amylase secretion from the acinar cell. This comprehensive view of the islet-acinar axis of the pancreas while acknowledging the dominant role played by insulin and somatostatin on exocrine secretion sheds light on the influence of the various neuropeptides on amylase secretion.

The efficacy of combining feG and galantide in mild caerulein-induced acute pancreatitis in mice.

We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection. feG was co-administered with the first injection of caerulein as a single intraperitoneal injection. Combination of the agents was also administered. Control animals received galantide, feG, or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma enzyme activities were measured. Galantide significantly reduced AP-induced hyperenzymemia by 41-49%. The combination of galantide and feG significantly reduced AP-induced hyperenzymemia by 39-40%, whereas feG alone was without effect. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide, feG, and their combination significantly reduced MPO activity by 83, 44 and 74% respectively, and % abnormal acinar cells by 32, 29 and 36% respectively. This study demonstrates for the first time the beneficial effect of feG in mild caerulein-induced AP. Moreover the data indicate that the hyperenzymemia in mild caerulein-induced AP at 12h possibly reflect a larger secretory component as compared to enzyme release due to neutrophil-mediated acinar cell damage. The effects of the treatment with both peptides indicate a possible role for galantide in modulating neutrophil chemotaxis/activation and supports the hypothesis that galantide may influence neurogenic inflammation in AP.

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

OBJECTIVES: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP. METHODS: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis. RESULTS: Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating. CONCLUSIONS: These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

The combination of neurokinin-1 and galanin receptor antagonists ameliorates caerulein-induced acute pancreatitis in mice.

Both galanin and substance P have been separately implicated in the pathogenesis of acute pancreatitis. We compared the efficacy of the combination of the galanin antagonist galantide and the neurokinin-1 receptor antagonist L703,606 with that of either alone in the treatment of acute pancreatitis. Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection (prophylactic) or 2h after the first injection (therapeutic). L703,606 was administered either 30 min before (prophylactic), or 2h after the first caerulein injection (therapeutic). Combination of the two agents was also administered. Control groups received galantide, L703,606, or saline, without caerulein. Pancreata were harvested for histological examination and estimation of myeloperoxidase activity. Plasma amylase activity was measured. Prophylactic and therapeutic administration of galantide reduced the hyperamylasemia by 37% and 30% respectively whereas only prophylactic L703,606 reduced hyperamylasemia (by 34%). Prophylactic administration of the combined antagonists reduced the hyperamylasemia by 44%. In contrast, therapeutic administration of the combination significantly increased plasma amylase levels by 27%. The plasma amylase activity in the control groups was similar to basal levels. Prophylactic and therapeutic administration of either antagonist or the combination significantly reduced myeloperoxidase activity. Galantide and L703,606 individually, and in combination, significantly reduced the acute pancreatitis-induced necrosis score. The administration of the combined antagonists does not offer any further benefit as compared to galantide alone. An interaction between neurokinin-1 and galanin receptors may occur to modulate amylase secretion.

Sphincter of Oddi: Function, dysfunction, and its management.

The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi. The Sphincter of Oddi is a small smooth muscle sphincter strategically placed at the junction of the bile duct, pancreatic duct, and duodenum. The sphincter controls flow of bile and pancreatic juices into the duodenum and prevents reflux of duodenal content into the ducts. Disorder in its motility is called Sphincter of Oddi dysfunction. Clinically this presents either with recurrent abdominal biliary type pain or episodes of recurrent pancreatitis. Manometry may identify the motility abnormalities, the most clinically significant being an abnormally elevated basal pressure. The most effective treatment once an abnormal basal pressure is identified is division of the sphincter. This is associated with good long-term results.

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion.

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10(-12)-10(-7) M) and caerulein (10(-7) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), diazoxide (10(-7) M), or the galanin antagonist galantide (10(-12)-10(-7) M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10(-12) M). Lobules were also coincubated with combinations of galanin (10(-12) M), caerulein, octreotide (10(-12)-10(-7) M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10(-9) M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10(-12)-10(-7) M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.