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Incretins

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https://www.readbyqxmd.com/read/28441725/sweet-taste-receptor-activation-in-the-gut-is-of-limited-importance-for-glucose-stimulated-glp-1-and-gip-secretion
#1
Monika Y Saltiel, Rune E Kuhre, Charlotte B Christiansen, Rasmus Eliasen, Kilian W Conde-Frieboes, Mette M Rosenkilde, Jens J Holst
Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin secretion from an isolated perfused rat small intestine and whether selective STR activation by artificial sweeteners stimulates secretion. Intra-luminal administration of the STR agonists, acesulfame K (3.85% w/v), but not sucralose (1...
April 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#2
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28435224/investigation-of-triamterene-as-an-inhibitor-of-the-tgr5-receptor-identification-in-cells-and-animals
#3
Yingxiao Li, Kai Chun Cheng, Chiang-Shan Niu, Shih-Hsiang Lo, Juei-Tang Cheng, Ho-Shan Niu
BACKGROUND: G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) has been shown to participate in glucose homeostasis. In animal models, a TGR5 agonist increases incretin secretion to reduce hyperglycemia. Many agonists have been developed for clinical use. However, the effects of TGR5 blockade have not been studied extensively, with the exception of studies using TGR5 knockout mice. Therefore, we investigated the potential effect of triamterene on TGR5. METHODS: We transfected the TGR5 gene into cultured Chinese hamster ovary cells (CHO-K1 cells) to express TGR5...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433470/daily-supplementation-of-dietary-protein-improves-the-metabolic-effects-of-glp-1-based-pharmacotherapy-in-lean-and-obese-rats
#4
Elizabeth G Mietlicki-Baase, Kieran Koch-Laskowski, Lauren E McGrath, Joanna Krawczyk, Tram Pham, Rinzin Lhamo, David J Reiner, Matthew R Hayes
Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and reduce feeding. Specific macronutrients, when ingested, may trigger GLP-1 secretion and enhance the effects of systemic sitagliptin, a pharmacological inhibitor of DPP-IV (an enzyme that rapidly degrades GLP-1). In particular, macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1, and acute preclinical trials show that ingestion of dairy protein may represent a promising adjunct behavioral therapy in combination with sitagliptin...
April 19, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#5
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28430907/food-intake-affects-sperm-egg-fusion-through-the-gip-psg17-axis-in-mice
#6
Tatsunori Shimizu, Takehiro Sato, Katsushi Tsukiyama, Hiroki Fujita, Shunsuke Kato, Manabu Hoizumi, Hiromitsu Shirasawa, Takuma Narita, Yukihiro Terada, Yutaka Seino, Yuichiro Yamada
In addition to overeating, starvation also reduces fecundity in mammals. However, little is known about the molecular mechanisms linking food intake to fertility, especially in males. Gastric inhibitory polypeptide (GIP), which is released from intestinal K-cells after meal ingestion, stimulates insulin secretion from pancreatic β-cells through the action of incretin and has several extra-pancreatic effects. Here, we identified GIP receptor (Gipr) expression in mouse spermatids. Microarray analysis revealed that pregnancy-specific glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly decreased in GIP receptor-knockout (Gipr-/-) testes...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28429513/distribution-and-hormonal-characterization-of-primary-murine-l-cells-throughout-the-gastrointestinal-tract
#7
Kazuyo Suzuki, Kanako Iwasaki, Yuki Murata, Norio Harada, Shunsuke Yamane, Akihiro Hamasaki, Kimitaka Shibue, Erina Joo, Akiko Sankoda, Yuta Fujiwara, Yoshitaka Hayashi, Nobuya Inagaki
AIMS/INTRODUCTION: Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells is an incretin that potentiates insulin secretion and is already applied in therapies for type 2 diabetes. However, detailed examination of L-cells throughout the gastrointestinal (GI) tract remains unclear, because of difficulties in purifying scattered L-cells from other cells. In the present study, we identified characteristics of L-cells of the upper small intestine (UI), the lower small intestine (LI) and the colon using glucagon (Gcg)-green fluorescent protein (GFP)-expressing mice that express GFP driven by the proglucagon promoter...
April 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28428027/fructose-intervention-for-12-weeks-does-not-impair-glycemic-control-or-incretin-hormone-responses-during-oral-glucose-or-mixed-meal-tests-in-obese-men
#8
N Matikainen, S Söderlund, E Björnson, L H Bogl, K H Pietiläinen, A Hakkarainen, N Lundbom, B Eliasson, S M Räsänen, A Rivellese, L Patti, A Prinster, G Riccardi, J-P Després, N Alméras, J J Holst, C F Deacon, J Borén, M-R Taskinen
BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. METHODS AND RESULTS: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle...
March 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28421793/effects-of-a-high-fat-meal-on-postprandial-incretin-responses-appetite-scores-and-ad-libitum-energy-intake-in-women-with-obesity
#9
Fernanda Rodrigues O Penaforte, Camila C Japur, Rosa W Diez-Garcia, Paula G Chiarello
BACKGROUND: Considering the possible role of triglycerides (TG), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the regulation of appetite, this study aimed to compare high fat meal-induced response of GIP and GLP-1, appetite scores and ad libitum energy intake in women with obesity, according to postprandial increment in triglyceridemia (∆TG).  Methods: Thirty-three no-diabetic women (BMI = 35.0 ± 3.2 kg.m-2) were divided into two groups: Group with ∆TG ≤ median were called "Low TG change -LTG" and ∆TG > median, "High TG change - HTG"...
March 30, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/28420649/a-sandwich-elisa-for-measurement-of-the-primary-glucagon-like-peptide-1-metabolite
#10
Nicolai J Wewer Albrechtsen, Ali Asmar, Frederik Jensen, Signe Törang, Lene Simonsen, Rune E Kuhre, Meena Asmar, Simon Veedfald, Astrid Plamboeck, Filip K Knop, Tina Vilsboll, Sten Madsbad, Michael A Nauck, Carolyn F Deacon, Jens Bulow, Jens J Holst, Bolette Hartmann
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects GLP-1 is secreted in its intact (active) form (7-36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9-36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9-36NH2 may have independent actions, and it is therefore relevant to be able to measure it...
April 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28413961/incretins-and-lipid-metabolism
#11
Vasilis Tsimihodimos, Moses S Elisaf
Backgound: Recent findings indicate that incretin hormones and incretin-based therapies may affect the metabolism of lipoproteins, although the corresponding mechanisms are not clearly defined. OBJECTIVE: To summarize the available data on the mechanisms linking incretins with the characteristics of serum lipoproteins and discuss the clinical implications of these relationships. METHODS: PubMed was searched using the terms "incretins", "GLP-1", "GIP" and "lipids", "dyslipidemia", "triglycerides", "apolipoprotein B48"...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28407474/the-impact-of-low-and-no-caloric-sweeteners-on-glucose-absorption-incretin-secretion-and-glucose-tolerance
#12
Catherine B Chan, Zohre Hashemi, Fatheema Begum Subhan
The consumption of non-nutritive, low or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance...
April 13, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#13
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
March 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28396144/supplementation-of-diet-with-galacto-oligosaccharides-increases-bifidobacteria-but-not-insulin-sensitivity-in-obese-prediabetic-individuals
#14
Emanuel E Canfora, Christina M van der Beek, Gerben D A Hermes, Gijs H Goossens, Johan W E Jocken, Jens J Holst, Hans M van Eijk, Koen Venema, Hauke Smidt, Erwin G Zoetendal, Cornelis H C Dejong, Kaatje Lenaerts, Ellen E Blaak
BACKGROUND & AIMS: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigate the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism. METHODS: We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m2) prediabetic men and women (ages, 45-70 years) from October 2014 through October 2015 in Maastricht, The Netherlands...
April 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28392300/glucagon-like-peptide-1-receptor-agonists-a-class-update-for-treating-type-2-diabetes
#15
REVIEW
Julie A Lovshin
Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia...
April 5, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28385801/mechanisms-controlling-glucose-induced-glp-1-secretion-in-human-small-intestine
#16
Emily W Sun, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L Due, David A Wattchow, Christopher K Rayner, Adam M Deane, Richard L Young, Damien J Keating
Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30 minute intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in ileum at 200mM glucose or above. In ex vivo tissue from duodenum and ileum, but not colon, 300mM glucose potently stimulated GLP-1 release...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28380367/pancreas-and-not-gut-mediates-the-glp-1-induced-glucoincretin-effect
#17
Joel F Habener, Violeta Stanojevic
The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28376896/regulation-of-visceral-and-epicardial-adipose-tissue-for-preventing-cardiovascular-injuries-associated-to-obesity-and-diabetes
#18
REVIEW
N González, Z Moreno-Villegas, A González-Bris, J Egido, Ó Lorenzo
Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy...
April 4, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28374974/mathematical-modelling-of-glucose-dependent-insulinotropic-polypeptide-and-glucagon-like-peptide-1-following-ingestion-of-glucose
#19
Rikke M Røge, Jonatan I Bagger, Oskar Alskär, Niels R Kristensen, Søren Klim, Jens J Holst, Steen H Ingwersen, Mats O Karlsson, Filip K Knop, Tina Vilsbøll, Maria C Kjellsson
The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting glucagon secretion and delaying gastric emptying. As the insulinotropic effect of GLP-1 is preserved in patients with type 2 diabetes (T2D), therapies based on GLP-1 have been developed in recent years, and these have proven to be efficient in the treatment of T2D...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28371189/effect-of-glp-1-and-gip-on-c-peptide-secretion-after-glucagon-or-mixed-meal-tests-significance-in-assessing-beta-cell-function-in-diabetes
#20
C Guglielmi, R Del Toro, A Lauria, A R Maurizi, A Cappelli, S Angeletti, J M Lachin, P Pozzilli
BACKGROUND: The aim of the study was to investigate the different β cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT). METHODS: We carried out GST and MMTT in 10 healthy people (aged 25-40 yrs) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon like peptide 1 (GLP1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT. RESULTS: The GST stimulated C-peptide showed a mean increase of 147...
March 31, 2017: Diabetes/metabolism Research and Reviews
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