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Laurentiu M Pop, Andrea Mari, Tong-Jin Zhao, Lori Mitchell, Shawn Burgess, Xilong Li, Beverley Adams-Huet, Ildiko Lingvay
AIM: To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux-en-Y Gastric Bypass (RYGB). In particular, the roles of concurrent peri-operative dietary restrictions, which may also alter glucose metabolism, have not been completely elucidated. MATERIALS AND METHODS: To assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled ten patients with type 2 diabetes scheduled to undergo RYGB...
March 13, 2018: Diabetes, Obesity & Metabolism
Cynthia Mohandas, Riccardo Bonadonna, Fariba Shojee-Moradie, Nicola Jackson, Linda Boselli, K George M M Alberti, Janet L Peacock, A Margot Umpleby, Stephanie A Amiel, Louise M Goff
AIMS: Populations of African ancestry suffer high rates of type 2 diabetes (T2D) compared to Caucasians. Phenotypic differences in pre-diabetic populations, particularly marked hyperinsulinaemia, suggest ethnic distinctions in T2D pathophysiology. We tested the hypothesis that men of Black (West) African (BAM) ethnicity with early T2D would have greater insulin secretory deficits compared to White Europeans (WEM), following the pre-diabetic hypersecretion. METHODS: In 19 BAM and 15 WEM, matched for age, BMI and duration diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test)...
March 8, 2018: Diabetes, Obesity & Metabolism
Caio E G Reis, Cicília L R Dos S Paiva, Angélica A Amato, Adriana Lofrano-Porto, Sara Wassell, Leslie J C Bluck, José G Dórea, Teresa H M da Costa
Epidemiological studies have found coffee consumption is associated with a lower risk for type 2 diabetes mellitus, but the underlying mechanisms remain unclear. Thus, the aim of this randomised, cross-over single-blind study was to investigate the effects of regular coffee, regular coffee with sugar and decaffeinated coffee consumption on glucose metabolism and incretin hormones. Seventeen healthy men participated in five trials each, during which they consumed coffee (decaffeinated, regular (containing caffeine) or regular with sugar) or water (with or without sugar)...
March 8, 2018: British Journal of Nutrition
Jae Hyun Bae, Lee Kyung Kim, Se Hee Min, Chang Ho Ahn, Young Min Cho
AIMS/INTRODUCTION: Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. This study was conducted to investigate the postprandial glucose-lowering effect of premeal protein-enriched, dietary fiber-fortified bar (PFB), which contains moderate amounts of protein, in subjects with type 2 diabetes mellitus (T2D) or normal glucose tolerance (NGT). MATERIALS AND METHODS: The participants (15 T2D and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests (MMTTs), 1 week apart in reverse order...
March 4, 2018: Journal of Diabetes Investigation
Wathik Alsalim, Margaretha Persson, Bo Ahrén
AIMS: Previous studies have shown that dipeptidyl peptidase (DPP)-4 inhibition lowers whereas sodium-glucose co-transporter 2 (SGLT-2) inhibition increases glucagon levels. This study evaluated the extent of these opposite effects in a direct comparative head-to-head study. METHODS: In a single-centre, randomized study with a cross-over design, 28 metformin-treated patients with type 2 diabetes (T2D; mean age 63 years, baseline HbA1c 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for two weeks with a four week wash out period in between...
March 2, 2018: Diabetes, Obesity & Metabolism
Anton M Pluschke, Barbara A Williams, Dagong Zhang, Stephen T Anderson, Eugeni Roura, Michael J Gidley
Acute and sustained soluble dietary fibre (SDF) consumption are both associated with improved glucose tolerance in humans and animal models (e.g. porcine). However, the effects on glucose tolerance in grower pigs, adapted to diets with a combination of SDF have not been studied previously. In this experiment, cereal SDF wheat arabinoxylan (AX) and oat β-glucan (BG) were fed individually and in combination to determine the effect on glucose tolerance in jugular vein catheterized grower pigs. Five groups of Large White male grower pigs were fed highly digestible diets containing either 10% AX, 10% BG, 5% AX with 5% BG, a model cereal whole wheat flour (WWF), or a control wheat starch diet (WS) with no SDF...
2018: PloS One
Oleg G Chepurny, Ron L Bonaccorso, Colin A Leech, Torsten Wöllert, George M Langford, Frank Schwede, Christian L Roth, Robert P Doyle, George G Holz
We report the design and target validation of chimeric peptide EP45, a novel 45 amino acid monomeric dual agonist peptide that contains amino acid sequence motifs present within the blood glucose-lowering agent exendin-4 (Ex-4) and the appetite-suppressing agent PYY(3-36). In a new high-throughput FRET assay that provides real-time kinetic information concerning levels of cAMP in living cells, EP45 recapitulates the action of Ex-4 to stimulate cAMP production via the glucagon-like peptide-1 receptor (GLP-1R), while also recapitulating the action of PYY(3-36) to inhibit cAMP production via the neuropeptide Y2 receptor (NPY2R)...
February 28, 2018: Scientific Reports
Jeroen S Kok, Marjan M A Nielen, Erik J A Scherder
BACKGROUND: Quality of life is a clinical highly relevant outcome for residents with dementia. The question arises whether small scaled homelike facilities are associated with better quality of life than regular larger scale nursing homes do. METHODS: A sample of 145 residents living in a large scale care facility were followed over 8 months. Half of the sample (N = 77) subsequently moved to a small scaled facility. Quality of life aspects were measured with the QUALIDEM and GIP before and after relocation...
February 27, 2018: Health and Quality of Life Outcomes
Tian Li, Juan-Juan Jiao, Christian Hölscher, Mei-Na Wu, Jun Zhang, Jia-Qing Tong, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Hong-Yan Cai, Qiang Su, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In the present study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms...
February 23, 2018: Hippocampus
Audrey Coreau, Jean-Baptiste Narcy, Sarah Lumbroso
The development of ecosystem knowledge is an essential condition for effective environmental management but using available knowledge to solve environmental controversies is still difficult in "real" situations. This paper explores the conditions under which ecological knowledge could contribute to the environmental strategies and actions of stakeholders at science-policy interface. Ecological restoration of the Seine estuary is an example of an environmental issue whose overall management has run into difficulties despite the production of a large amount of knowledge by a dedicated organization, GIP Seine Aval...
February 22, 2018: Environmental Management
Songyan Wang, Lauren Z Oestricker, Michael J Wallendorf, Karin Sterl, Judit Dunai, C Rachel Kilpatrick, Bruce W Patterson, Dominic N Reeds, Burton M Wice
We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice...
2018: PloS One
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM...
February 17, 2018: Neuropharmacology
Nam Q Nguyen, Tamara L Debreceni, Jenna E Burgess, Max Bellon, Judith Wishart, Scott Standfield, Charles-Henri Malbert, Michael Horowitz
This study evaluated gastric emptying (GE) and small intestinal (SI) transit in people with morbid obesity and their relationships to glycaemia, incretin hormones, and glucose absorption METHODS: GE and caecal arrival time (CAT) of a mixed meal were assessed in 22 morbidly obese (50.2 ± 2.5 years; 13 F:9 M; BMI: 48.6 ± 1.8 kg/m2 ) and 10 lean (38.6 ± 8.4 years; 5 F:5 M; BMI: 23.9 ± 0.7 kg/m2 ) subjects, using scintigraphy. Blood glucose, plasma 3-O-methylglucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Ghaith Al-Badri, Gian Marco Leggio, Giuseppe Musumeci, Rubina Marzagalli, Filippo Drago, Alessandro Castorina
Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide (GIP), three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells...
January 2018: Neural Regeneration Research
Tanya J Little, Nada Cvijanovic, Nicholas V DiPatrizio, Donovan A Argueta, Christopher K Rayner, Christine Feinle-Bisset, Richard L Young
INTRODUCTION/AIMS: Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion...
February 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Pawel Antoni Kolodziejski, Maciej Sassek, Daniela Chalupka, Natalia Leciejewska, Leszek Nogowski, Pawel Mackowiak, Damian Jozefiak, Katarzyna Stadnicka, Maria Siwek, Marek Bednarczyk, Tomasz Szwaczkowski, Ewa Pruszynska-Oszmalek
Background: In order to discover new strategies to replace antibiotics in the post-antibiotic era in meat-type chicken production, two new synbiotics were tested: (Lactobacillus salivarius IBB3154 plus galactooligosaccharide (Syn1) and Lactobacillus plantarum IBB3036 plus raffinose family oligosaccharides (Syn2). Methods: The synbiotics were administered via syringe, using a special automatic system, into the egg air chamber of Cobb 500 broiler chicks on the 12th day of egg incubation (2 mg of prebiotics + 105 cfu bacteria per egg)...
2018: Journal of Animal Science and Biotechnology
Varun Pathak, Peter R Flatt, Nigel Irwin
Cholecystokinin (CCK) is a hormone secreted from I-cells of the gut, as well as neurons in the enteric and central nervous system, that binds and activates CCK-1 and CCK-2 receptors to mediate its biological actions. To date knowledge relating to the physiological significance of CCK has predominantly focused around induction of short-term satiety. However, CCK has also been highlighted to possess important actions in relation to the regulation of insulin secretion, as well as overall beta-cell function and survival...
February 2018: Peptides
Annie Hasib, Ming T Ng, Dawood Khan, Victor A Gault, Peter R Flatt, Nigel Irwin
Combined modulation of peptide hormone receptors including, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and xenin, have established benefits for the treatment of diabetes. The present study has assessed the biological actions and therapeutic efficacy of a novel exendin-4/xenin-8-Gln hybrid peptide, both alone and in combination with the GIP receptor agonist (DAla2)GIP. Exendin-4/xenin-8-Gln was enzymatically stable and exhibited enhanced insulin secretory actions when compared to its parent peptides...
February 2018: Peptides
Sara J Brandt, Anna Götz, Matthias H Tschöp, Timo D Müller
Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies...
February 2018: Peptides
Lærke Smidt Gasbjerg, Maria Buur Nordskov Gabe, Bolette Hartmann, Mikkel Bring Christensen, Filip Krag Knop, Jens Juul Holst, Mette Marie Rosenkilde
Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone with a broad range of physiological actions. In the postprandial state, the hormone stimulates insulin secretion and during eu- and hypoglycemia, it stimulates glucagon secretion. In addition, GIP increases triacylglycerol (TAG) uptake in adipose tissue and decreases bone resorption. However, the importance of these actions in humans are not clearly understood as a specific GIP receptor (GIPR) antagonist - an essential tool to study GIP physiology - has been missing...
February 2018: Peptides
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