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Diabetes AND glp-1

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https://www.readbyqxmd.com/read/28645541/comparison-of-the-effect-by-which-gastric-plication-and-sleeve-gastrectomy-procedures-alter-metabolic-and-physical-parameters-in-an-obese-type-2-diabetes-rodent-model
#1
Min Ye, Renhong Huang, Zhijun Min, Peng Zhang, Tingfeng Wang, Bo Yu
BACKGROUND: Gastric plication (GP) and sleeve gastrectomy (SG) are 2 restrictive bariatric surgeries that are associated with weight loss and health improvement in patients with obesity. However, differences in how these procedures exert their effects have not been systematically evaluated and compared between techniques. OBJECTIVES: To investigate the effectiveness of GP and SG surgeries for obese patients with type 2 diabetes based on evaluation of energy metabolism, hormone metabolism, and gastrointestinal dynamics...
May 11, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28643293/-why-is-a-combination-of-basal-insulin-with-a-glp-1-receptor-agonist-useful-in-many-patients-with-type-2-diabetes
#2
Michael Nauck, Birgit Wilhelm
BACKGROUND: In 2015, the combination of basal insulin and GLP-1 receptor agonist (RA) was incorporated into the guideline recommendations for type 2 diabetes as an option for the last escalation step. The two antidiabetics to be injected subcutaneously are complementary regarding their respective main effects and limitations. Basal insulin is predominantly active between meals and in the fasting state, whereas the main action of GLP-1 RA consists in preventing an excessive postprandial blood glucose increase...
June 2017: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/28642113/paralog-divergent-features-may-help-reduce-off-target-effects-of-drugs-hints-from-glucagon-subfamily-analysis
#3
Zhining Sa, Jingqi Zhou, Yangyun Zou, Zhixi Su, Xun Gu
Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes...
June 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#4
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#5
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#6
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28630069/degradation-of-incretins-and-modulation-of-blood-glucose-levels-by-periodontopathic-bacterial-dipeptidyl-peptidase-4
#7
Yuko Ohara-Nemoto, Manami Nakasato, Yu Shimoyama, Tomomi T Baba, Takeshi Kobayakawa, Toshio Ono, Takashi Yaegashi, Shigenobu Kimura, Takayuki K Nemoto
Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28627773/oleanolic-acid-derivative-dks26-exerts-antidiabetic-and-hepatoprotective-effects-in-diabetic-mice-and-promotes-glp-1-secretion-and-expression-in-intestinal-cells
#8
Fei-Fei Chen, Jian-Ta Wang, Li-Xia Zhang, Shu-Fang Xing, Yun-Xia Wang, Kai Wang, Shu-Li Deng, Ji-Quan Zhang, Lei Tang, Hao-Shu Wu
BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP-1 related antidiabetic mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: The therapeutic effects of DKS26 were inspected in streptozotocin (STZ)-induced and db/db diabetic mouse models including levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro-inflammation cytokines...
June 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28626167/a-human-glucagon-like-peptide-1-albumin-recombinant-protein-with-prolonged-hypoglycemic-effect-provides-efficient-and-beneficial-control-of-glucose-metabolism-in-diabetic-mice
#9
Caina Li, Miaomiao Yang, Guojiang Hou, Shuainan Liu, Yi Huan, Dongan Yu, Sujuan Sun, Quan Liu, Shousheng Yan, Zhufang Shen
GW002 is a recombinant protein engineered by fusing the C-terminal region of human glucagon-like peptide-1 (GLP-1) to the N-terminal region of human serum albumin (HSA) with a peptide linker. This study aims to evaluate its anti-diabetic effects both in vitro and vivo. The GLP-1 receptor-dependent luciferase reporter plasmid was transiently transfected in NIT-1 cells to calculate the half-maximal concentration (EC50) for GLP-1 receptor activation, and normal ICR mice and diabetic KKAy mice were acutely injected with GW002 (1, 3 and 9 mg/kg) subcutaneously to evaluate the hypoglycemic action, while the diabetic KKAy and db/db mice were treated with GW002 once daily for 7 weeks to evaluate the effects on glucose metabolism...
June 17, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28625506/long-term-cost-effectiveness-of-two-glp-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus-in-the-italian-setting-liraglutide-versus-lixisenatide
#10
Barnaby Hunt, Nana Kragh, Ceilidh C McConnachie, William J Valentine, Maria C Rossi, Roberta Montagnoli
PURPOSE: Maintaining glycemic control is the key treatment target for patients with type 2 diabetes mellitus. In addition, the glucagon-like peptide-1 (GLP-1) receptor agonists may be associated with other favorable treatment characteristics, such as reduction in body weight and reduced risk of hypoglycemia compared with traditional diabetes interventions. The aim of the present analysis was to compare the long-term cost-effectiveness of 2 GLP-1 receptor agonists, liraglutide 1.8 mg and lixisenatide 20 μg (both administered once daily), in the treatment of patients with type 2 diabetes failing to achieve glycemic control with metformin monotherapy in the Italian setting...
June 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28624122/glucagon-like-peptide-1-and-insulin-synergistically-activate-vagal-afferent-neurons
#11
Yusaku Iwasaki, Chayon Goswami, Toshihiko Yada
Intestinal glucagon-like peptide-1 (GLP-1) and pancreatic insulin, released postprandially, commonly regulate glucose metabolism. Recent clinical experience indicates that the GLP-1R agonist and insulin in combination, compared to insulin alone, results in better glycemic and weight controls in type 2 diabetic patients. These observations suggest possible interactive effect of these hormones. These hormones, in addition to peripherally controlling glycemia, exert central regulation of food intake and glucose metabolism, the effect at least partly mediated by signaling to the brain via the vagal afferents...
May 25, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28622905/discovery-of-novel-somatostatin-receptor-subtype-5-sstr5-antagonists-pharmacological-studies-and-design-to-improve-pharmacokinetic-profiles-and-human-ether-a-go-go-related-gene-herg-inhibition
#12
Takeshi Yamasaki, Hideki Hirose, Tohru Yamashita, Nobuyuki Takakura, Sachie Morimoto, Takashi Nakahata, Asato Kina, Yoshihide Nakano, Yumiko Okano Tamura, Jun Sugama, Tomoyuki Odani, Yuji Shimizu, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin (SST) is a peptide hormone comprising 14 or 28 amino acids that inhibits endocrine and exocrine secretion via five distinct G-protein-coupled receptors (SSTR1-5). SSTR5 has an important role in inhibiting the secretion of pancreatic and gastrointestinal hormones (e.g., insulin, GLP-1, PYY) through the binding of SSTs; hence, SSTR5 antagonists are expected to be novel anti-diabetic drugs. In the course of our lead generation program of SSTR5 antagonists, we have discovered a novel spiroazetidine derivative 3a...
June 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28619366/bpi-3016-a-novel-long-acting-hglp-1-analogue-for-the-treatment-of-type-2-diabetes-mellitus
#13
Lieming Ding, Sisi Lu, Yanping Wang, Haibo Chen, Wei Long, Cunbo Ma, Erlong He, Dan Yan, Fenlai Tan
Glucagon-like peptide-1 (GLP-1) analogues have been commonly used as add-on medications for patients with Type 2 diabetes mellitus (T2DM). Currently, the development of long-acting GLP-1 analogues which allow the freedom and flexibility of once-weekly injections while maintaining their potency for a relatively long period has become the mainstream. Here, we successfully developed a long-acting human GLP-1(7-37) analogue (BPI-3016) with significantly extended half-life and increased resistance to dipeptidyl peptidase IV (DPP-IV) cleavage by structural modifications of human GLP-1...
June 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28616805/effects-of-insulin-plus-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-treating-type-1-diabetes-mellitus-a-systematic-review-and-meta-analysis
#14
REVIEW
Weihao Wang, Hongyan Liu, Shumin Xiao, Shuaihui Liu, Xin Li, Pei Yu
INTRODUCTION: Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) has already been proven an efficient treatment option for type 2 diabetes. This combination can effectively improve glycated hemoglobin levels, cause weight loss and reduce the dosage of insulin. In addition, it can also reduce the risk of hypoglycemia. Several randomized controlled trials have confirmed that this treatment may be just as effective for type 1 diabetes mellitus (T1DM) patients...
June 14, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28611211/metabolic-and-neuroprotective-effects-of-dapagliflozin-and-liraglutide-in-diabetic-mice
#15
Paul Millar, Nupur Pathak, Vadivel Parthsarathy, Tony Bjourson, Maurice O'Kane, Varun Pathak, R Charlotte Moffett, Peter R Flatt, Victor A Gault
This study assessed the metabolic and neuroprotective actions of the sodium glucose co-transporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy x-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined...
June 13, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28610922/central-administration-of-glp-1-and-gip-decreases-feeding-in-mice
#16
Cherl NamKoong, Min Sun Kim, Byeong-Tak Jang, Young Hee Lee, Young-Min Cho, Hyung Jin Choi
Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28609478/purification-of-family-b-g-protein-coupled-receptors-using-nanodiscs-application-to-human-glucagon-like-peptide-1-receptor
#17
Yingying Cai, Yuting Liu, Kelly J Culhane, Brian T DeVree, Yang Yang, Roger K Sunahara, Elsa C Y Yan
Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e...
2017: PloS One
https://www.readbyqxmd.com/read/28609372/pancreatic-polypeptide-cell-proliferation-in-the-pancreas-and-duodenum-coexisting-in-a-patient-with-pancreatic-adenocarcinoma-treated-with-a-glp-1-analog
#18
Geoffrey A Talmon, J David Wren, Christophe L Nguyen, Parviz M Pour
A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28608285/the-glp-1-analogue-lixisenatide-decreases-atherosclerosis-in-insulin-resistant-mice-by-modulating-macrophage-phenotype
#19
Ángela Vinué, Jorge Navarro, Andrea Herrero-Cervera, Marta García-Cubas, Irene Andrés-Blasco, Sergio Martínez-Hervás, José T Real, Juan F Ascaso, Herminia González-Navarro
AIMS/HYPOTHESIS: Recent clinical studies indicate that glucagon-like peptide-1 (GLP-1) analogues prevent acute cardiovascular events in type 2 diabetes mellitus but their mechanisms remain unknown. In the present study, the impact of GLP-1 analogues and their potential underlying molecular mechanisms in insulin resistance and atherosclerosis are investigated. METHODS: Atherosclerosis development was evaluated in Apoe (-/-) Irs2 (+/-) mice, a mouse model of insulin resistance, the metabolic syndrome and atherosclerosis, treated with the GLP-1 analogues lixisenatide or liraglutide...
June 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28605280/the-gut-a-key-to-the-pathogenesis-of-type-2-diabetes
#20
Jens Juul Holst, Jens Pedersen, Nicolai Jacob Wewer Albrechtsen, Filip Krag Knop
In this communication we discuss the role of the gut for the development of type 2 diabetes mellitus (T2DM). Gastric emptying rates importantly determine postprandial glucose excursions and regulate postprandial secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). It thereby also determines their powerful, amplifying effect on glucose-induced insulin secretion and thus the ability of the body to regulate glucose disposal. Although disturbances in gastric emptying are not consistent findings in type 2 diabetes, the incretin system is seriously impaired, probably associated with insulin resistance and obesity...
June 12, 2017: Metabolic Syndrome and related Disorders
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