M. Michael Wolfe

Gastric inhibitory polypeptide immunoneutralization attenuates development of obesity in mice.

Previous reports have suggested that the abrogation of gastric inhibitory polypeptide (GIP) signaling could be exploited to prevent and treat obesity and obesity-related disorders in humans. This study was designed to determine whether immunoneutralization of GIP, using a newly developed specific monoclonal antibody (mAb), would prevent the development of obesity. Specific mAb directed against the carboxy terminus of mouse GIP was identified, and its effects on the insulin response to oral and to intraperitoneal (ip) glucose and on weight gain were evaluated. Administration of mAb (30 mg/kg body wt, BW) to mice attenuated the insulin response to oral glucose by 70% and completely eliminated the response to ip glucose coadministered with human GIP. Nine-week-old C57BL/6 mice injected with GIP mAbs (60 mg·kg BW(-1)·wk(-1)) for 17 wk gained 46.5% less weight than control mice fed an identical high-fat diet (P < 0.001). No significant differences in the quantity of food consumed were detected between the two treatment groups. Furthermore, magnetic resonance imaging demonstrated that subcutaneous, omental, and hepatic fat were 1.97-, 3.46-, and 2.15-fold, respectively, lower in mAb-treated animals than in controls. Moreover, serum insulin, leptin, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides were significantly reduced, whereas the high-density lipoprotein (HDL)/TC ratio was 1.25-fold higher in treated animals than in controls. These studies support the hypothesis that a reduction in GIP signaling using a GIP-neutralizing mAb might provide a useful method for the treatment and prevention of obesity and related disorders.

Optimal Omeprazole Dosing and Symptom Control: A Randomized Controlled Trial (OSCAR Trial)

BackgroundProton pump inhibitors (PPIs) are potent inhibitors of acid secretion and are the mainstay of therapy for gastroesophageal reflux disease (GERD). Initially designed to be taken 30xa0min before the first daily meal, these agents are commonly used suboptimally, which adversely affects symptom relief. No study to date has assessed whether correcting dosing regimens would improve symptom control. The objective of this study was to determine whether patients with persistent GERD symptoms on suboptimal omeprazole dosing experience symptomatic improvement when randomized to commonly recommended dosing regimen and to evaluate the economic impact of suboptimal PPI dosing in GERD patients.MethodsPatients with persistent heartburn symptomsu2009≥u20093 times per week treated with omeprazole 20xa0mg daily were enrolled and randomized to commonly recommended dosing or continued suboptimal dosing of omeprazole. The primary outcomes were changes in symptom, frequency, and severity, as determined using the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) 4 weeks after the intervention was administered. In secondary analysis, an alternative measure of symptom load was used to infer potential costs.ResultsSixty-four patients were enrolled. GSAS symptom, frequency, and severity scores were significantly better when dosing was optimized for overall and heartburn-specific symptoms (Pu2009<u20090.01 for all parameters). Cost savings resulting from reduced medical care and workplace absenteeism were estimated to be

GI Peptides, Energy Balance, and Cancer

159.60 per treated patient, with cost savings potentially exceeding

Su1129 Optimal Omeprazole Dosing and Symptom Control - A Randomized Controlled Trial (OSCAR Trial)

4 billion annually in the USA.DiscussionLow-cost efforts to promote commonly recommended PPI dosing can dramatically reduce GERD symptoms and related economic costs.ClinicalTrials.gov, number: NCT02623816.

Prevention and treatment of nonalcoholic fatty liver disease (NAFLD) by antagonism of the receptor to glucose-dependent insulinotropic polypeptide (GIP)

Beyond its role in nutrient absorption, the gastrointestinal tract is a vital endocrine organ responsible for the production of a variety of regulatory peptides that modulate energy balance. In this chapter, the most studied gastrointestinal peptides are described, with emphasis on their roles played in appetite control, glucose homeostasis, and weight disorders. Translational research investigating drug development targeting the “gut–brain” axis regulatory pathway for the treatment of obesity and diabetes is also highlighted. Several GI peptides have proliferative and/or pro-apoptotic functions and their possible cancer-related effects are discussed.

TREATMENT OR REPLACEMENT THERAPY USING TRANSGENIC STEM CELLS DELIVERED TO THE GUT

Background nProton pump inhibitors (PPIs) are potent inhibitors of acid secretion and are the mainstay of therapy for gastroesophageal reflux disease (GERD). Initially designed to be taken 30 min before the first daily meal, these agents are commonly used suboptimally, which adversely affects symptom relief. No study to date has assessed whether correcting dosing regimens would improve symptom control. The objective of this study was to determine whether patients with persistent GERD symptoms on suboptimal omeprazole dosing experience symptomatic improvement when randomized to commonly recommended dosing regimen and to evaluate the economic impact of suboptimal PPI dosing in GERD patients.