CONTEXT AND OBJECTIVE:Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth.PATIENTS AND METHODS:We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts.RESULTS:Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients.CONCLUSION:A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Obesity imposes devastating health and financial tolls on society and those who suffer from it. Despite the growing awareness of the problem, the obesity epidemic, along with its associated complications, continues to expand at an alarming rate (1). The current nomenclature used to measure an individuals degree of obesity is BMI, which is calculated by dividing weight (in kilograms) by the square of height (in meters) (Table 1). Based on these criteria, the CDC (Centers for Disease Control and Prevention) reports a doubling of the obese population (BMI ≥30 kg/m2) in the period between 1976–1980 and 2001–2002 to reach an estimated number of 63 million obese people. Currently in the U.S., nearly two-thirds of adults are overweight (BMI >25 kg/m2), nearly one-third are considered obese (BMI ≥30 kg/m2), and 4.7% are extremely obese (BMI ≥40 kg/m2) (2). The financial cost of obesity in the U.S. is estimated to be in excess of $100 billion/year (3). In addition to increased risk of diabetes and other comorbid diseases, obese individuals may expect significant decreases in life expectancy (4) (Table 2). This obesity-related diminution in longetivity directly contributes to 280,000 deaths annually in the U.S. (5).Medical (nonsurgical) weight loss therapies include combinations of diet, exercise, behavioral therapies, and medications. In 1998, an NIH (National Institutes of Health) expert panel, upon critical review of the literature, concluded that these modalities, either alone or in combination, can induce modest weight loss that confers health benefits to the patients (6). However, the weight loss induced by these therapies is often short lived. Furthermore, medical management must continue indefinitely to be effective, or weight regain is common. Such medical therapies have not been shown to be effective in maintaining long-term weight loss in a morbidly obese patient population. Thus, most physicians …

Aims/hypothesis Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive to diet, octreotide and diazoxide with the aim of elucidating the pathological mechanisms involved. Methods Glucose, insulin, and C-peptide were measured in the fasting and postprandial state, and insulin secretion was assessed following selective intra-arterial calcium injection. Pancreas histopathology was assessed in all three patients. Results All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control of neuroglycopenia; pancreas pathology of all patients revealed diffuse islet hyperplasia and expansion of beta cell mass. Conclusions/interpretation These findings suggest that gastric bypass-induced weight loss may unmask an underlying beta cell defect or contribute to pathological islet hyperplasia, perhaps via glucagon-like peptide 1-mediated pathways.

Obesity is the single most significant risk factor for the development of nonalcoholic fatty liver disease (NAFLD) in children and adults. NALFD is estimated to occur in 30 to 100% of obese adults, and in approximately 53% of obese children. The majority of obese patients have ultrasonographic evidence of fatty liver; 30% have histologically documented nonalcoholic steatohepatitis (NASH). Up to 25% of patients with NASH may progress to cirrhosis. In the United States, an estimated 65% of adults are overweight and 31% are obese. Between 2001 and 2002, the number of people with severe obesity, who are more than 100 pounds overweight, rose to nearly 11 million. Since 1970, levels of childhood and teen overweight have climbed to approximately 16% in those aged 6 to 19 years. Recent findings indicate that key features of NAFLD and NASH improve or resolve dramatically with weight loss. This article discusses weight loss surgeries and their effects on liver disease.

Journal of Laparoendoscopic & Advanced Surgical TechniquesVol. 13, No. 4 Original PapersLaparoscopic Gastric Bypass Surgery: OutcomesBenjamin E. Schneider, Leonardo Villegas, George L. Blackburn, Edward C. Mun, Jonathan F. Critchlow, and Daniel B. JonesBenjamin E. Schneider, Leonardo Villegas, George L. Blackburn, Edward C. Mun, Jonathan F. Critchlow, and Daniel B. JonesPublished Online:7 Jul 2004https://doi.org/10.1089/109264203322333575AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited BySingle anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S): experience from a high-bariatric volume center29 March 2022 | Langenbeck's Archives of Surgery, Vol. 407, No. 5Laparoscopic Gastric BypassSurgical Clinics of North America, Vol. 101, No. 2High Rates of Nicotine Use Relapse and Ulcer Development Following Roux-en-Y Gastric Bypass22 September 2020 | Obesity Surgery, Vol. 31, No. 2Chronic Abdominal Pain After Previous Bariatric Surgery: Consider the Abdominal Wall27 April 2020 | Obesity Surgery, Vol. 30, No. 8Gastric Bypass Complications12 November 2019Bariatric Surgery and Its Complications in Inflammatory Bowel Disease Patients18 October 2019 | Inflammatory Bowel Diseases, Vol. 384Surgery for Acute Bariatric Complications22 June 2019MagenManagement of Post-Bariatric ComplicationsLate postoperative bleeding after Roux-en-Y gastric bypass: management and review of literature9 December 2018 | BMJ Case Reports, Vol. 11, No. 1Factors Associated with Recurrent Ulcers in Patients with Gastric Surgery after More Than 15 Years: A Cross-Sectional Single-Center StudyGastroenterology Research and Practice, Vol. 2018The incidence of complications associated with loop duodeno-ileostomy after single-anastomosis duodenal switch procedures among 1328 patients: a multicenter experienceSurgery for Obesity and Related Diseases, Vol. 14, No. 5Stricture Following Gastric Bypass and Vertical Sleeve Gastrectomy27 April 2018When the Surgeon Needs the Endoscopist in Rescuing Bariatric Surgery: Intermediate and Late Post-operative Period28 November 2018Endoscopic Evaluation/Management of Bariatric Surgery Complications10 November 2017 | Current Treatment Options in Gastroenterology, Vol. 15, No. 4Gastric interventional endoscopyCurrent Opinion in Gastroenterology, Vol. 33, No. 6Complications of Bariatric Surgery: What You Can Expect to See in Your GI PracticeAmerican Journal of Gastroenterology, Vol. 112, No. 11Vertical Gastric Bypass with Fundectomy: Feasibility and 2-Year Follow-Up in a Series of Morbidly Obese Patients7 March 2017 | Obesity Surgery, Vol. 27, No. 8Review article including treatment algorithm: endoscopic treatment of luminal complications after bariatric surgery15 February 2017 | Clinical Obesity, Vol. 7, No. 2Prevention and Management of Marginal Ulcers3 February 2017Low Prevalence of Clinically Significant Endoscopic Findings in Outpatients with DyspepsiaGastroenterology Research and Practice, Vol. 2017Obesity: Presentations and Management Options1 August 2016Surgical Complications of Weight Loss Surgery2 April 2015Complications chirurgicales du by-pass gastrique dans les hôpitaux Neuchâtelois (Suisse)5 February 2014 | Obésité, Vol. 9, No. 2Development of Ulcer Disease After Roux-en-Y Gastric Bypass, Incidence, Risk Factors, and Patient Presentation: A Systematic Review14 November 2013 | Obesity Surgery, Vol. 24, No. 2Endoscopic Management of Complications After Gastrointestinal Weight Loss SurgeryClinical Gastroenterology and Hepatology, Vol. 11, No. 4Endoscopic Management of Post-Bariatric Foreign Bodies: Dysfunctional Sutures, Staples, and Bands27 December 2012Bariatric Surgery30 July 2012Surgical Treatment of Obesity23 May 20122. Laparoscopic Roux-en-Y Gastric Bypass: Techniques and Outcomes27 February 2012Clinical Outcomes of the Marginal Ulcer Bleeding after Gastrectomy: As Compared to the Peptic Ulcer Bleeding with Nonoperated StomachGastroenterology Research and Practice, Vol. 2012References4 May 2011Laparoscopic Mini-gastric Bypass for Type 2 Diabetes: The Preliminary Report17 December 2010 | World Journal of Surgery, Vol. 35, No. 3BAROS results in 700 patients after laparoscopic Roux-en-Y gastric bypass with subset analysis of age, gender, and initial body mass indexSurgery for Obesity and Related Diseases, Vol. 7, No. 1Laparoscopic revision of gastrojejunostomy revision with truncal vagotomy for persistent marginal ulcer after Roux-en-Y gastric bypassSurgery for Obesity and Related Diseases, Vol. 6, No. 5Removing foreign bodies in bariatric patientTechniques in Gastrointestinal Endoscopy, Vol. 12, No. 3Bariatric surgery: techniques, outcomes and complicationsCurrent Anaesthesia & Critical Care, Vol. 21, No. 1Benchmarking Best Practices in Weight Loss SurgeryCurrent Problems in Surgery, Vol. 47, No. 2Les complications de la chirurgie bariatriqueSituación actual de la derivación gástrica laparoscópicaDerivación gástrica laparoscópica con endograpadora circularSurgical Management of Gastroesophageal Reflux Disease in Obesity29 July 2008 | Digestive Diseases and Sciences, Vol. 53, No. 9A Perioperative Team Approach to Treating Patients Undergoing Laparoscopic Bariatric SurgeryAORN Journal, Vol. 88, No. 1DiscussionPlastic and Reconstructive Surgery, Vol. 119, No. 6Postoperative Assessment, Documentation, and Follow-Up of Bariatric Roux-en-Y Surgical PatientsLaparoscopic Roux-en-Y Gastric Bypass: OutcomesSurgical Treatment for the Overweight PatientCurrent Status of Laparoscopic Gastric BypassLaparoscopic Gastric Bypass Using the Circular StaplerUse of double-balloon enteroscopy to perform PEG in the excluded stomach after Roux-en-Y gastric bypassGastrointestinal Endoscopy, Vol. 64, No. 5Laparoscopic Surgery for ObesityAsian Journal of Surgery, Vol. 29, No. 4Length of stay and impact on readmission rates after laparoscopic gastric bypassSurgery for Obesity and Related Diseases, Vol. 2, No. 4Laparoscopic bariatric surgery16 March 2006 | Surgical Endoscopy, Vol. 20, No. S2Incidence of marginal ulcers and the use of absorbable anastomotic sutures in laparoscopic Roux-en-Y gastric bypassSurgery for Obesity and Related Diseases, Vol. 2, No. 1Surgery for Obesity: Panacea or Pandora's Box?8 August 2006 | Digestive Surgery, Vol. 23, No. 1-2Techniques of Laparoscopic Gastric Bypass16 April 2013Gastric bypass for severe obesity: Approaches and outcomesSurgery for Obesity and Related Diseases, Vol. 1, No. 3Surgical Management of Morbid ObesityDiabetes Care, Vol. 28, No. 2Laparoscopic Roux-en-Y gastric bypass procedure for morbid obesity: OutcomesSurgery for Obesity and Related Diseases, Vol. 1, No. 1Effect of Bariatric Surgery on Long-term MortalityAdvances in Surgery, Vol. 39Surgical Treatment of the Overweight PatientSurgical Treatment of Obesity and Diabetes Volume 13Issue 4Aug 2003 To cite this article:Benjamin E. Schneider, Leonardo Villegas, George L. Blackburn, Edward C. Mun, Jonathan F. Critchlow, and Daniel B. Jones.Laparoscopic Gastric Bypass Surgery: Outcomes.Journal of Laparoendoscopic & Advanced Surgical Techniques.Aug 2003.247-255.http://doi.org/10.1089/109264203322333575Published in Volume: 13 Issue 4: July 7, 2004PDF download

BACKGROUND:Luminal fluid sequestration and diarrhea are early manifestations of mesenteric ischemia. This can be modeled in vitro with the use of T84 intestinal epithelia, where ischemia induces Cl(-) secretion with adenosine-mediated autocrine feedback. Protein kinase C (PKC) regulates epithelial transport and, in some organ systems, is involved in the response to ischemic stress. The purpose of this study was to define the role of PKC on epithelial transport during ischemia. METHODS:By voltage-current clamp, short-circuit current (Isc) equals Cl(-) secretion. Ischemic conditions were simulated with the use of a well-established chemical hypoxia protocol. RESULTS:Chemical hypoxia briskly activated Isc. Gö6850, an antagonist of novel and conventional PKC isoforms, markedly enhanced the ischemia-induced Isc response, although Gö6976 (which inhibits only conventional isoforms) had no effect. Rottlerin, a specific inhibitor of PKC delta, did not attenuate ischemic Isc. Both phorbol 12-myristate, 13-acetate and bryostatin-1, which selectively activate PKC epsilon in T84 cells, markedly attenuated the Isc response to ischemia. Both agents also inhibited the Isc response to exogenous adenosine. CONCLUSIONS:PKC (likely the novel epsilon isoform) in intestinal epithelia modulates ischemia-induced alterations in ion transport. Inhibition of PKC epsilon exaggerates the secretory response that is induced by ischemia and by authentic adenosine; conversely, augmented activation of PKC epsilon inhibits secretion. Manipulation of PKC epsilon could limit luminal fluid sequestration during mesenteric ischemia.

Levamisole (LEV) weakly activates CFfR, the apical Cl channel of cAMP-mediated Cl secretion, via effects on an alkaline phosphatase.Despite activating CFrR, we found that LEV inhibits

Levamisole (LEV) weakly activates CFfR, the apical Cl channel of cAMP-mediated Cl secretion, via effects on an alkaline phosphatase.Despite activating CFrR, we found that LEV inhibits

The basolateral Na+/K+/2Cl− cotransporter (NKCC1) has been shown to be an independent regulatory site for electrogenic Cl− secretion. The proinflammatory phorbol ester, phorbol 12‐myristate 13‐acetate (PMA), which activates protein kinase C (PKC), inhibits basal and cyclic adenosine monophosphate (cAMP)‐stimulated NKCC1 activity in T84 intestinal epithelial cells and decreases the steady state levels of NKCC1 mRNA in a time‐ and dose‐dependent manner. The levels of NKCC1 protein also fall in accordance with the NKCC1 mRNA transcript and these levels are unaffected by 4α‐phorbol, which does not activate PKC. Inhibition of maximal (cAMP‐stimulated) NKCC1 functional activity by PMA was first detected by 1 h, whereas decreases in the steady state levels of NKCC1 mRNA were not detectable until 4 h. NKCC1 mRNA expression recovers toward control levels with extended treatment of cells with PMA suggesting that the PMA effects on NKCC1 expression are mediated through activation of PKC. Although NKCC1 mRNA and protein levels return to control values after extended PMA exposure, NKCC1 functional activity does not recover. Immunofluorescence imaging suggest that the absence of functional recovery is due to failure of newly synthesized NKKC1 protein to reach the cell surface. We conclude that NKCC1 has the capacity to be regulated at the level of de novo expression by PKC, although decreased NKCC1 expression alone cannot account for either early or late loss of NKCC1 function. J. Cell. Physiol. 181:489–498, 1999. © 1999 Wiley‐Liss, Inc.

Adenosine release from mucosal sources during inflammation and ischemia activates intestinal epithelial Cl- secretion. Previous data suggest that A(2b) receptor-mediated Cl- secretory responses may be dampened by epithelial cell nucleoside scavenging. The present study utilizes isotopic flux analysis and nucleoside analog binding assays to directly characterize the nucleoside transport system of cultured T84 human intestinal epithelial cells and to explore whether adenosine transport is regulated by secretory agonists, metabolic inhibition, or phorbol ester. Uptake of adenosine across the apical membrane displayed characteristics of simple diffusion. Kinetic analysis of basolateral uptake revealed a Na+-independent, nitrobenzylthioinosine (NBTI)-sensitive facilitated-diffusion system with low affinity but high capacity for adenosine. NBTI binding studies indicated a single population of high-affinity binding sites basolaterally. Neither forskolin, 5'-(N-ethylcarboxamido)-adenosine, nor metabolic inhibition significantly altered adenosine transport. However, phorbol 12-myristate 13-acetate significantly reduced both adenosine transport and the number of specific NBTI binding sites, suggesting that transporter number may be decreased through activation of protein kinase C. This basolateral facilitated adenosine transporter may serve a conventional function in nucleoside salvage and a novel function as a regulator of adenosine-dependent Cl- secretory responses and hence diarrheal disorders.

BACKGROUND & AIMS:Phenylimidazothiazoles have recently been shown to activate wild-type and mutant cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels in transfected cells and were proposed as therapy for cystic fibrosis. The aim of this study was to investigate the effects of phenylimidazothiazoles on regulated transepithelial Cl- transport in intact epithelia. METHODS:T84 intestinal epithelial cells grown on permeable supports and stripped human colonic mucosal sheets were studied by conventional current-voltage clamping. Selective permeabilization of apical or basolateral membranes with the monovalent ionophore nystatin was used to isolate basolateral K+ and apical Cl- channel activity, respectively. 86Rb+ uptake was assessed for Na/K/2Cl cotransporter and Na+,K(+)-adenosine triphosphatase activity. RESULTS:In T84 monolayers and human colon, levamisole and its brominated derivative bromotetramisole failed to activate transepithelial secretion. In fact, these compounds dose-dependently inhibited secretory responses to the cyclic adenosine monophosphate agonist forskolin and the Ca2+ agonist carbachol. In permeabilized T84 monolayers, phenylimidazothiazoles weakly activated apical Cl- currents (consistent with their reported action on CFTR) and did not affect bumetanide-sensitive or bumetanide-insensitive 86+Rb+ uptake. Instead, they profoundly inhibited the basolateral Ba(2+)-sensitive and Ba(2+)-insensitive K+ currents. CONCLUSIONS:Phenylimidazothiazoles block K+ channels required for Cl(-)-secretory responses elicited by diverse pathways in model epithelia and native colon, an effect that outweighs their ability to activate apical Cl- channels.

The sigma ligand igmesine (JO 1784) has been shown to act on nerves to inhibit intestinal ion transport in the isolated mouse jejunumL The present study evaluates the ability of igmesine to inhibit the VIP-induced jejunal hypersecretion in rats and investigates the possibility of the involvement of endogenous somatostatin in the response to igmesine.Methods: In anesthetized (pentobarbital, 60 mg/kg i.p.) fasted Sprague-Dawley rats (160-180 g), a jejunal loop was isolated by two ligations at 5 and 25 cm distal to the ligament of Treitz.The loop was filled with saline (2 ml, 37°C).Jejunal secretion was stimulated by a 30 min intraarterial infusion of VIP.At the end of the VIP infusion, the loop was collected, measured and weighed before and after fluid removal to determine water net flux (mg/cm).Intravenous (i.v.) bolus injections of igmesine or octreotide were performed 15 min before starting VIP infusion.Tetrodotoxin (TTX) at 5 mg/kg, the somatosatin antagonist, cyclosomatostatin (CSS) at 1 mg/kg, or the sigma antagonist, BMY-14802 (BMY) at 1 mg/kg were given by i.v.route 5 min before igmesine or octreotide.Results: In the basal state the net water flux was positive (+3.13 ±3.9 mg/cm).VIP (0.03-0.33 mg.min -1) induced a dose-related inversion of net flux.The submaximal effect (-34.1 -+ 7.1 mg/cm) was obtained at the dose of 0.1 mg.min -1.VIP (0.1 mg.min -1) induced jejunal hypersecretion was inhibited in a doserelated manner by igmesine and octreotide (EDso: 178 and 0.132 mg/kg i.v., respectively).Igmesine (1 mg/kg) and octreotide (1 mg/kg) responses were inhibited by TTX (-96% and -45%, respectively) and CSS (-88% and -100%, respectively).BMY abolished the igmesine response but did not alter the octreotide response.TI'X, CSS and BMY did not alterper se the VIP response.Conclusion: The VIP response was blocked by Igmesine in a TTX-, CSS-and BMY-sensitive manner, suggesting an indirect action on the enterocyte through sigma receptors, nerve-and somatostatin-pathways.Octreotide response was BMY-insensitive indicating that somatostatin receptors activated during the Igmesine response are likely to be distal to the sigma receptors.