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GLP-1 AND adipocyte

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https://www.readbyqxmd.com/read/29094257/the-effects-of-exendin-4-on-bone-marrow-derived-mesenchymal-cells
#1
Paola Luciani, Benedetta Fibbi, Benedetta Mazzanti, Cristiana Deledda, Lara Ballerini, Alessandra Aldinucci, Susanna Benvenuti, Riccardo Saccardi, Alessandro Peri
PURPOSE: GLP-1 receptor agonists are antidiabetic drugs currently used in the therapy of type 2 diabetes. Despite several in vitro and in vivo animal studies suggesting a beneficial effect of GLP-1 analogues on bone, in humans their skeletal effects are not clear and clinical studies report conflicting results. METHODS: We differentiated human mesenchymal stromal cells (hMSC) toward the adipogenic and the osteoblastic lineages, analysing the effect of Exendin-4 (EXE) before, during and after specific differentiations...
November 1, 2017: Endocrine
https://www.readbyqxmd.com/read/29066599/il-6-type-cytokine-signaling-in-adipocytes-induces-intestinal-glp-1-secretion
#2
Stephan Wueest, Céline I Laesser, Marianne Böni-Schnetzler, Flurin Item, Fabrizio C Lucchini, Marcela Borsigova, Werner Müller, Marc Y Donath, Daniel Konrad
We recently showed that IL-6-type cytokine signaling in adipocytes induces FFA release from visceral adipocytes thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by that means induce GLP-1 secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high fat diet for 12 weeks...
October 24, 2017: Diabetes
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#3
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#4
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28668964/glp-1-glp-1r-signaling-in-regulation-of-adipocyte-differentiation-and-lipogenesis
#5
Jicui Chen, Huichen Zhao, Xiaoli Ma, Yuchao Zhang, Sumei Lu, Yangang Wang, Chen Zong, Dandan Qin, Yuanmei Wang, Yingfeng Yingfeng Yang, Xiangdong Wang, Yuantao Liu
BACKGROUND/AIMS: The aim of this study was to determine the direct role of liraglutide (LG) in adipogenesis and lipid metabolism. METHODS: Lipid accumulation was evaluated by oil red O staining, quantitative real-time PCR (qPCR) was performed to determine glucagon-like peptide 1 receptor (GLP-1R), fatty acid synthase (FASN) and adipose triglyceride lipase (ATGL) expression in 3T3-L1 preadipocytes, differentiated adipocytes and in adipose tissues from mice. The effects of LG on 3T3-L1 adipogenesis and lipid metabolism were analyzed with qPCR, Western Blotting, oil red O staining, immunohistochemistry (IHC) and immunofluorescence (IF)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28555111/novel-glp-1-analog-supaglutide-reduces-hfd-induced-obesity-associated-with-increased-ucp-1-in-white-adipose-tissue-in-mice
#6
Yun Wan, Xi Bao, Jiabao Huang, Xiangyu Zhang, Wenjuan Liu, Qiaoli Cui, Dongdong Jiang, Zhihong Wang, Rui Liu, Qinghua Wang
GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28523587/erratum-to-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-the-brain-adipocyte-axis
#7
Bruno Geloneze, José Carlos de Lima-Júnior, Lício A Velloso
No abstract text is available yet for this article.
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#8
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
August 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28347868/teneligliptin-a-dipeptidyl-peptidase-4-inhibitor-attenuated-pro-inflammatory-phenotype-of-perivascular-adipose-tissue-and-inhibited-atherogenesis-in-normoglycemic-apolipoprotein-e-deficient-mice
#9
Hotimah Masdan Salim, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Michio Shimabukuro, Masataka Sata
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0...
September 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28166771/glycemic-insulinemic-and-incretin-responses-after-oral-trehalose-ingestion-in-healthy-subjects
#10
Chiyo Yoshizane, Akiko Mizote, Mika Yamada, Norie Arai, Shigeyuki Arai, Kazuhiko Maruta, Hitoshi Mitsuzumi, Toshio Ariyasu, Shimpei Ushio, Shigeharu Fukuda
BACKGROUND: Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers...
February 6, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/28122026/exendin-4-upregulates-adiponectin-level-in-adipocytes-via-sirt1-foxo-1-signaling-pathway
#11
Anping Wang, Ting Li, Ping An, Wenhua Yan, Hua Zheng, Baoan Wang, Yiming Mu
Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/27704740/correlation-of-glypican-4-level-with-basal-active-glucagon-like-peptide-1-level-in-patients-with-type-2-diabetes-mellitus
#12
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
https://www.readbyqxmd.com/read/27504979/glucagon-like-peptide-1-promotes-adipocyte-differentiation-via-the-wnt4-mediated-sequestering-of-beta-catenin
#13
Rui Liu, Na Li, Yi Lin, Mei Wang, Yongde Peng, Keidren Lewi, Qinghua Wang
Glucagon-like peptide-1 (GLP-1) plays a role in the regulation of adipogenesis; however, the precise underlying molecular mechanism has not been fully defined. Wnt was recently identified as an important regulator of adipogenesis. This study aimed to investigate the involvement of the Wnt signaling pathway in the effects of GLP-1 on adipocyte differentiation. 3T3-L1 cells were induced to differentiate. The changes in the expression levels of adipogenic transcription factors and Wnts and the phosphorylation level and subcellular localization of β-catenin were quantified after GLP-1 treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27385588/a-novel-allosteric-activator-of-free-fatty-acid-2-receptor-displays-unique-gi-functional-bias
#14
Daniele Bolognini, Catherine E Moss, Karolina Nilsson, Annika U Petersson, Iona Donnelly, Eugenia Sergeev, Gabriele M König, Evi Kostenis, Mariola Kurowska-Stolarska, Ashley Miller, Niek Dekker, Andrew B Tobin, Graeme Milligan
The short chain fatty acid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fatty acid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11 Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant...
September 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27333994/changes-in-levels-of-biomarkers-associated-with-adipocyte-function-and-insulin-and-glucagon-kinetics-during-treatment-with-dapagliflozin-among-obese-type-2-diabetes-mellitus-patients
#15
Aki Okamoto, Hirohide Yokokawa, Hironobu Sanada, Toshio Naito
OBJECTIVES: This study aimed to investigate changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics after a meal tolerance test (MTT) during treatment with dapagliflozin among obese type 2 diabetes mellitus (T2DM) patients. METHODS: T2DM patients with hemoglobin A1c (HbA1c) levels >6.5 % and body mass index (BMI) >25 kg/m(2) were treated with dapagliflozin 5 mg/day for at least 12 weeks. HbA1c, body weight, ketone bodies, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) were measured before and after treatment with dapagliflozin...
September 2016: Drugs in R&D
https://www.readbyqxmd.com/read/27186360/novel-extrapancreatic-effects-of-incretin
#16
REVIEW
Yuichiro Yamada, Katsushi Tsukiyama, Takehiro Sato, Tatsunori Shimizu, Hiroki Fujita, Takuma Narita
The hormonal factors implicated as transmitters of signals from the gut to pancreatic β-cells are referred to as incretins. Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretins. In addition to the insulinotropic effects, we have shown, using the GIP receptor and GLP-1 receptor-deficient mice, that GIP and GLP-1 have direct actions on adipocytes and the kidney, respectively. Because GIP receptors and GLP-1 receptors are differentially expressed in a tissue-specific manner, GIP and GLP-1 have specific physiological activities, and further comprehensive characterization of the extrapancreatic actions of GIP and GLP-1 is anticipated, as dipeptidyl peptidase IV inhibitors activate both GIP and GLP-1 signaling...
April 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/26993859/effects-of-glucagon-like-peptide-1-on-the-differentiation-and-metabolism-of-human-adipocytes
#17
Rajaa El Bekay, Leticia Coín-Aragüez, Diego Fernández-García, Wilfredo Oliva-Olivera, Rosa Bernal-López, Mercedes Clemente-Postigo, Javier Delgado-Lista, Alberto Diaz-Ruiz, Rocío Guzman-Ruiz, Rafael Vázquez-Martínez, Said Lhamyani, María Mar Roca-Rodríguez, Sonia Fernandez Veledo, Joan Vendrell, María M Malagón, Francisco José Tinahones
No abstract text is available yet for this article.
June 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26974159/pi3-kinase-mutation-linked-to-insulin-and-growth-factor-resistance-in-vivo
#18
Jonathon N Winnay, Marie H Solheim, Ercument Dirice, Masaji Sakaguchi, Hye-Lim Noh, Hee Joon Kang, Hirokazu Takahashi, Kishan K Chudasama, Jason K Kim, Anders Molven, C Ronald Kahn, Pål R Njølstad
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in the gene encoding the p85α regulatory subunit of PI3K (PIK3R1) have been identified in patients with SHORT syndrome - a disorder characterized by short stature, partial lipodystrophy, and insulin resistance. Here, we evaluated whether SHORT syndrome-associated PIK3R1 mutations account for the pathophysiology that underlies the abnormalities by generating knockin mice that are heterozygous for the Pik3r1Arg649Trp mutation, which is homologous to the mutation found in the majority of affected individuals...
April 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26971825/glucose-dependent-insulinotropic-peptide-stimulates-glucagon-like-peptide-1-production-by-pancreatic-islets-via%C3%A2-interleukin-6-produced-by-%C3%AE-cells
#19
Katharina Timper, Elise Dalmas, Erez Dror, Sabine Rütti, Constanze Thienel, Nadine S Sauter, Karim Bouzakri, Benoit Bédat, Francois Pattou, Julie Kerr-Conte, Marianne Böni-Schnetzler, Marc Y Donath
BACKGROUND & AIMS: Glucose-dependent insulinotropic peptide (GIP) induces production of interleukin 6 (IL6) by adipocytes. IL6 increases production of glucagon-like peptide (GLP)-1 by L cells and α cells, leading to secretion of insulin from β cells. We investigated whether GIP regulates GLP1 and glycemia via IL6. METHODS: We obtained samples of human pancreatic islets and isolated islets from mice; human α cells and β cells were sorted by flow cytometry and incubated with GIP...
July 2016: Gastroenterology
https://www.readbyqxmd.com/read/26947974/activation-of-glp-1-receptor-promotes-bone-marrow-stromal-cell-osteogenic-differentiation-through-%C3%AE-catenin
#20
Jingru Meng, Xue Ma, Ning Wang, Min Jia, Long Bi, Yunying Wang, Mingkai Li, Huinan Zhang, Xiaoyan Xue, Zheng Hou, Ying Zhou, Zhibin Yu, Gonghao He, Xiaoxing Luo
Glucagon-like peptide 1 (GLP-1) plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4) promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased...
April 12, 2016: Stem Cell Reports
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