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Monica L Castro-Acosta, Leanne Smith, Rosalind J Miller, Danielle I McCarthy, Jonathan A Farrimond, Wendy L Hall
Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14M, 9W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal...
September 14, 2016: Journal of Nutritional Biochemistry
Sharareh Monemi, Erhan Berber, Khaled Sarsour, Jianmei Wang, Kathy Lampl, Kamal Bharucha, Attila Pethoe-Schramm
INTRODUCTION: The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA). METHODS: Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept...
July 15, 2016: Rheumatol Ther
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
Yong Zhang, Xiaoguang Li, Jiamin Li, Qingwei Zhang, Xiaohui Chen, Xin Liu, Yue Zhang, Haiying Zhang, Huan Yang, Yingying Hu, Xianxian Wu, Xin Li, Jiaming Ju, Baofeng Yang
Diabetes mellitus (DM) is a metabolic disorder manifested by hyperglycemia. Daming Capsule (DMC), a combination of traditional Chinese herbs, is used clinically as a lipid-lowering drug. This study was designed to evaluate if DMC possesses an anti-hyperglycemic effect and to elucidate the underlying mechanisms. Compared to diabetic rats, the rats received DMC (200 mg/kg/d) had significantly lower blood lipid and glucose levels. DMC markedly restored the decreased secretion of GLP-1 and GIP as well as the coding gene GCG and GIP in ileum...
October 10, 2016: Scientific Reports
Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst
AIMS/HYPOTHESIS: GLP-1 receptor agonists and DPP-4 inhibitors both stimulate GLP-1 receptors. Our objective was to determine, whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. METHODS: 16 subjects with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥ 2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (a) sitagliptin (100 mg p...
October 6, 2016: Diabetes, Obesity & Metabolism
Sang Ah Lee, Gwanpyo Koh, Suk Ju Cho, So Yeon Yoo, Sang Ouk Chin
BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)...
September 2016: Endocrinology and Metabolism
Miguel Angel Sánchez-Garrido, Kirk M Habegger, Christoffer Clemmensen, Cassie Holleman, Timo D Müller, Diego Perez-Tilve, Pengyun Li, Archita S Agrawal, Brian Finan, Daniel J Drucker, Matthias H Tschöp, Richard D DiMarchi, Alexei Kharitonenkov
OBJECTIVE: Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling...
October 2016: Molecular Metabolism
Zhong Chen, Xiaoying Fu, Jian Kuang, Ju Chen, Hongmei Chen, Jianhao Pei, Huazhang Yang
BACKGROUND: Acarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: In this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n = 11) and the mixed meal test (MMT) group (n = 12)...
September 29, 2016: BMC Endocrine Disorders
Aine M McKillop, Brian M Moran, Yasser H A Abdel-Wahab, Noella M Gormley, Peter R Flatt
AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0...
September 27, 2016: Diabetologia
Chao Kang, Yong Zhang, Xiaohui Zhu, Kai Liu, Xiaolan Wang, Mengting Chen, Jian Wang, Hua Chen, Suocheng Hui, Li Huang, Qianyong Zhang, Jundong Zhu, Bin Wang, Mantian Mi
CONTEXT: Previous population studies in evaluating the beneficial effects of capsaicin (CAP) have yielded inconclusive results, and the mechanisms responsible for possible benefit remain unclear. OBJECTIVE: The objective was to assess the impact of dietary CAP on metabolic and immune profiles and its potential associations with gut microbial patterns in healthy adults. DESIGN: In a 6-week controlled feeding trial, subjects were given the weight maintenance diet sequentially contained with 0, 5, 0 and 10 mg/d CAP from chili powder...
September 27, 2016: Journal of Clinical Endocrinology and Metabolism
Isabel Comino, Fernando Fernández-Bañares, María Esteve, Luís Ortigosa, Gemma Castillejo, Blanca Fambuena, Carmen Ribes-Koninckx, Carlos Sierra, Alfonso Rodríguez-Herrera, José Carlos Salazar, Ángel Caunedo, J M Marugán-Miguelsanz, José Antonio Garrote, Santiago Vivas, Oreste Lo Iacono, Alejandro Nuñez, Luis Vaquero, Ana María Vegas, Laura Crespo, Luis Fernández-Salazar, Eduardo Arranz, Victoria Alejandra Jiménez-García, Marco Antonio Montes-Cano, Beatriz Espín, Ana Galera, Justo Valverde, Francisco José Girón, Miguel Bolonio, Antonio Millán, Francesc Martínez Cerezo, César Guajardo, José Ramón Alberto, Mercé Rosinach, Verónica Segura, Francisco León, Jorge Marinich, Alba Muñoz-Suano, Manuel Romero-Gómez, Ángel Cebolla, Carolina Sousa
OBJECTIVES: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. METHODS: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls...
October 2016: American Journal of Gastroenterology
Sadek Ismail, Marie-Julie Gherardi, Alexander Froese, Madjid Zanoun, Véronique Gigoux, Pascal Clerc, Frederique Gaits-Iacovoni, Jan Steyaert, Viacheslav O Nikolaev, Daniel Fourmy
Until very recently, G-protein dependent signal of GPCRs was thought to originate exclusively from the plasma membrane and internalized GPCRs were considered silent. Here, we demonstrated that, once internalized and located in the membrane of early endosomes, glucose-dependent Insulinotropic receptor (GIPR) continues to trigger production of cAMP and PKA activation. Direct evidence is based on identification of the active form of Gαs in early endosomes containing GIPR using a genetically encoded GFP tagged nanobody, and on detection of a distinct FRET signal accounting for cAMP production at the surface of endosomes containing GIP, compared to endosomes without GIP...
September 15, 2016: Biochemical Pharmacology
Kazunari Kamiko, Kazutaka Aoki, Hiroshi Kamiyama, Masataka Taguri, Yasuo Terauchi
BACKGROUND: A fast eating speed is reportedly associated with obesity, fatty liver, and metabolic syndrome. As a comparison of postprandial glucose levels after eating quickly or slowly has not been previously reported for Japanese patients with type 2 diabetes, we evaluated the impact of the fast or slow ingestion of an enteral formula (liquid meal) on glucose metabolism. METHODS: Ten Japanese patients with type 2 diabetes who had been hospitalized at our hospital were enrolled...
October 2016: Journal of Clinical Medicine Research
(no author information available yet)
AIMS/HYPOTHESIS: The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study...
September 13, 2016: Diabetologia
Lijuan Sun, Kevin Wei Jie Tan, Phei Ching Siow, Christiani Jeyakumar Henry
Apart from the well-known action of insulin, the mechanism by which soya and cows' milk improve postprandial glycaemia control was examined. In total, twelve healthy, young, Chinese men were studied on three separate occasions, in random order with isovolumetric (322 ml) control water, soya milk and cows' milk. Plasma total amino acid concentrations increased 30 min after test meals consumption and were higher after soya milk (230 %) and cow milk (240 %) consumption compared with water. Cows' milk ingestion induced higher branched-chain amino acids (BCAA) (40 %) than soya milk...
October 2016: British Journal of Nutrition
Brian M Moran, Aine M McKillop, Finbarr Pm O'Harte
Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119)...
September 5, 2016: Current Opinion in Pharmacology
Tongzhi Wu, Xiang Zhang, Laurence G Trahair, Michelle J Bound, Tanya J Little, Carolyn F Deacon, Michael Horowitz, Karen L Jones, Christopher K Rayner
CONTEXT: The rate of gastric emptying is an important determinant of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion, and may influence the magnitude of glucose-lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors. OBJECTIVE: To evaluate the effects of the DPP-4 inhibitor, vildagliptin, during intraduodenal (ID) glucose infusion at two different rates within the physiological range of gastric emptying, in type 2 diabetes...
September 6, 2016: Journal of Clinical Endocrinology and Metabolism
Ying Wang, Jintang Du, Huafei Zou, Yan Liu, Yuhan Zhang, Jose Gonzalez, Elizabeth Chao, Lucy Lu, Pengyu Yang, Holly Parker, Van Nguyen-Tran, Weijun Shen, Danling Wang, Peter G Schultz, Feng Wang
Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), glucagon (GCG) receptor (GCGR), and glucose-dependent insulinotropic polypeptide (GIP, also known as gastric inhibitory polypeptide) receptor (GIPR), are three metabolically related peptide hormone receptors. A novel approach to the generation of multifunctional antibody agonists that activate these receptors has been developed. Native or engineered peptide agonists for GLP-1R, GCGR, and GIPR were fused to the N-terminus of the heavy chain or light chain of an antibody, either alone or in pairwise combinations...
September 26, 2016: Angewandte Chemie
Ying Wang, Aleksey Lomakin, Sonoko Kanai, Rainer Alex, Sara Belli, Massimiliano Donzelli, George B Benedek
Hybrid incretin peptides are a new generation of drugs for the treatment of diabetes and obesity. Despite their biological potency, the effectiveness of these peptides as drugs is limited by their short circulation time in blood (typically within minutes). In this work, we show that lipid conjugated forms of a GLP-1/GIP/glucagon hybrid peptides stay in circulation for hours. We studied the oligomerization and albumin-binding of the unconjugated hybrid peptide as well as its lipidated variants. These lipidated peptides differ in the N-terminal mutation, the position of lipidation and the linkage to lipid...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
R Sekar, K Singh, A W R Arokiaraj, B K C Chow
Glucagon family of peptide hormones is a group of structurally related brain-gut peptides that exert their pleiotropic actions through interactions with unique members of class B1 G protein-coupled receptors (GPCRs). They are key regulators of hormonal homeostasis and are important drug targets for metabolic disorders such as type-2 diabetes mellitus (T2DM), obesity, and dysregulations of the nervous systems such as migraine, anxiety, depression, neurodegeneration, psychiatric disorders, and cardiovascular diseases...
2016: International Review of Cell and Molecular Biology
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