Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet.

Pancreatic β-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is known to be involved in high-fat diet (HFD)-induced obesity, the effect of GIP on BCM is still controversial.

Clinical practice guidelines for endoscopic papillectomy.

The Japan Gastroenterological Endoscopy Society has developed the "Clinical Practice Guidelines for Endoscopic Papillectomy (EP)" as a fundamental guideline using scientific approach. EP is a recently spreading therapeutic modality for ampullary tumors ranked as high risk endoscopic technique. Because of the paucity of high level of evidence, strength of recommendations had to be determined by a consensus among specialists.

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas.

Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [F]FB(ePEG12)12-exendin-4 (F-Ex4) for PET imaging.

Distinctive detection of insulinoma using [F]FB(ePEG12)12-exendin-4 PET/CT.

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

Aims/introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy.

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with In-labeled exendin-4.

Radiolabeled exendin derivatives are promising for non-invasive quantification of pancreatic beta cell mass (BCM); longitudinal observation of BCM for evaluation of therapeutic effects has not been achieved. The aim of this study is to demonstrate the usefulness of our developing method using [Lys(In-BnDTPA-Ahx)]exendin-4 to detect longitudinal changes in BCM. We performed a longitudinal study with obese type 2 diabetes model (db/db) mice administered canagliflozin, which is reported to preserve BCM.

Noninvasive Evaluation of GPR119 Agonist Effects on β-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT.

Longitudinal observation of pancreatic β-cell mass (BCM) remains challenging because noninvasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus, a progressive disease involving loss of pancreatic BCM and function. An indium 111 (111In)-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) targeting the glucagon-like peptide-1 receptor has been developed recently as a promising probe for quantifying the BCM noninvasively.

Noninvasive longitudinal quantification of β-cell mass with [In]-labeled exendin-4.

Currently, quantifying β-cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using [Lys(In-BnDTPA-Ahx)]exendin-4 ([In]-Ex4) and single-photon emission computed tomography (SPECT). We used autoradiography and transgenic mice expressing green fluorescent protein under the control of mouse insulin 1 gene promotor to evaluate the specificity of [In]-Ex4 toward β cells.

Clinical practice guidelines for safe performance of endoscopic ultrasound/ultrasonography-guided biliary drainage: 2018.

Endoscopic ultrasound/ultrasonography-guided biliary drainage (EUS-BD) is a relatively new modality for biliary drainage after failed or difficult transpapillary biliary cannulation. Despite its clinical utility, EUS-BD can be complicated by severe adverse events such as bleeding, perforation, and peritonitis. The aim of this paper is to provide practice guidelines for safe performance of EUS-BD as well as safe introduction of the procedure to non-expert centers.

Establishment of a method for in-vivo SPECT/CT imaging analysis of In-labeled exendin-4 pancreatic uptake in mice without the need for nephrectomy or a secondary probe.

Introduction: Radiolabeled exendin derivatives have been developed to visualize and quantify pancreatic beta cells. However, there are currently no established methods for analyzing in-vivo SPECT/CT images to quantify probe accumulation in the pancreas in rodent models. In this study, we aimed to establish an analytical method for murine in-vivo SPECT/CT imaging.

Japan Gastroenterological Endoscopy Society guidelines for endoscopic papillary large balloon dilation.

The Japan Gastroenterological Endoscopy Society has developed the 'EPLBD Clinical Practice Guidelines' as fundamental guidelines based on new scientific techniques. EPLBD is a treatment method that has recently become widely used for choledocolithiasis. The evidence level in this field is usually low, and in many instances, the recommendation grading has to be determined on the basis of expert consensus.

Evaluation of F-labeled exendin(9-39) derivatives targeting glucagon-like peptide-1 receptor for pancreatic β-cell imaging.

β-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed.

Japan Gastroenterological Endoscopy Society guidelines for endoscopic sphincterotomy.

The Japan Gastroenterological Endoscopy Society (JGES) has recently compiled guidelines for endoscopic sphincterotomy (EST) using evidence-based methods. Content regarding actual clinical practice, including detailed endoscopic procedures, instruments, device types and usage, has already been published by the JGES postgraduate education committee in May 2015 and, thus, in these guidelines we avoided duplicating such content as much as possible. The guidelines do not address pancreatic sphincterotomy, endoscopic papillary balloon dilation (EPBD), and endoscopic papillary large balloon dilation (EPLBD).

Synthesis and biological evaluation of an In-labeled exendin-4 derivative as a single-photon emission computed tomography probe for imaging pancreatic β-cells.

A non-invasive method of pancreatic β-cell mass measurement is needed to enhance our understanding of the pathogenesis of diabetes, facilitate the early diagnosis of this disease, and promote the development of novel therapeutics. Here, we described the synthesis of a novel indium-111 (In) exendin-4 derivative, [Lys(In-BnDTPA-Ahx)]exendin-4, through a process involving isothiocyanate-benzyl-DTPA (BnDTPA) and 6-aminohexanoic acid (Ahx) attached to an ɛ-amino group at the lysine-12 residue. We further evaluated the potential use of this derivative as a SPECT probe for pancreatic β-cell imaging.

Real-life glycemic control in patients with type 2 diabetes treated with insulin therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 9]).

Aims/introduction: We investigated the association between four insulin regimens, and increase in glycated hemoglobin (HbA1c) and insulin dose in a real-life clinical setting because there are no data about them among insulin regimens.

Materials And Methods: Participants included 757 patients with type 2 diabetes having been treated with insulin therapy for more than 1 year. The four insulin regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic insulin, twice daily), regimen 3 (biphasic insulin, three times daily) and regimen 4 (basal-bolus therapy).

Current status of interventional endoscopic ultrasound.

Endoscopic ultrasound (EUS) is being used increasingly in the management of pancreatic fluid collection, biliary and pancreatic duct drainage in cases of failed endoscopic retrograde cholangiopancreatography, drainage of the gallbladder, and other conditions. The role of interventional EUS is rapidly expanding and new interventions are continuously emerging. The development of devices could be a major breakthrough in the field of interventional EUS.

Development of In-labeled exendin(9-39) derivatives for single-photon emission computed tomography imaging of insulinoma.

Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist.

Evidence-based clinical practice guidelines for cholelithiasis 2016.

Cholelithiasis is one of the commonest diseases in gastroenterology. Remarkable improvements in therapeutic modalities for cholelithiasis and its complications are evident. The Japanese Society of Gastroenterology has revised the evidence-based clinical practice guidelines for cholelithiasis.

Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-Inflammatory Cytokine Expression in Liver of Diabetic ob/ob Mice.

Procyanidins, the main ingredient of apple polyphenols, are known to possess antioxidative and anti-inflammatory effects associated closely with the pathophysiology of insulin resistance and type 2 diabetes. We investigated the effects of orally administered apple procyanidins (APCs) on glucose metabolism using diabetic ob/ob mice. We found no difference in body weight or body composition between mice treated with APCs and untreated mice.

Carbon dioxide insufflation in esophageal endoscopic submucosal dissection reduces mediastinal emphysema: A randomized, double-blind, controlled trial.

Aim: To assess the efficacy of CO2 insufflation for reduction of mediastinal emphysema (ME) immediately after endoscopic submucosal dissection (ESD).

Methods: A total of 46 patients who were to undergo esophageal ESD were randomly assigned to receive either CO2 insufflation (CO2 group, n = 24) or air insufflation (Air group, n = 22). Computed tomography (CT) was carried out immediately after ESD and the next morning.