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GLP-1 AND adipocyte

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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
#1
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
#2
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
#3
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...
April 25, 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
#4
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...
March 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28166771/glycemic-insulinemic-and-incretin-responses-after-oral-trehalose-ingestion-in-healthy-subjects
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/26924394/glp-1-receptor-agonist-promotes-brown-remodelling-in-mouse-white-adipose-tissue-through-sirt1
#16
Fen Xu, Beisi Lin, Xiaobin Zheng, Zonglan Chen, Huanyi Cao, Haixia Xu, Hua Liang, Jianping Weng
AIMS/HYPOTHESIS: Accumulating evidence has revealed the significant role of glucagon-like peptide-1 (GLP-1) in weight loss. Sirtuin 1 (SIRT1) plays a vital role in the regulation of lipid metabolism. Here, we investigated the contribution of lipolytic and oxidative changes in white adipose tissue (WAT) to the weight-lowering effect induced by the GLP-1 receptor (GLP-1R) agonist exenatide (exendin-4) in mice. We also looked at the role of SIRT1 in this process. METHODS: C57BL/6J mice and Sirt1 (+/-) mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i...
May 2016: Diabetologia
https://www.readbyqxmd.com/read/26794660/inhibition-of-the-map3-kinase-tpl2-protects-rodent-and-human-%C3%AE-cells-from-apoptosis-and-dysfunction-induced-by-cytokines-and-enhances-anti-inflammatory-actions-of-exendin-4
#17
E M Varin, A Wojtusciszyn, C Broca, D Muller, M A Ravier, F Ceppo, E Renard, J-F Tanti, S Dalle
Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression locus 2 (Tpl2) is known to integrate signals from inflammatory stimuli in macrophages, fibroblasts and adipocytes, its role in β-cells is unknown. We demonstrate that Tpl2 is expressed in INS-1E β-cells, mouse and human islets, is activated and upregulated by cytokines and mediates ERK1/2, JNK and p38 activation...
January 21, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/26741352/practical-prospects-for-boosting-hepatic-production-of-the-pro-longevity-hormone-fgf21
#18
Mark F McCarty
Fibroblast growth factor-21 (FGF21), produced mainly in hepatocytes and adipocytes, promotes leanness, insulin sensitivity, and vascular health while down-regulating hepatic IGF-I production. Transgenic mice overexpressing FGF21 enjoy a marked increase in median and maximal longevity comparable to that evoked by calorie restriction - but without a reduction in food intake. Transcriptional factors which promote hepatic FGF21 expression include PPARα, ATF4, STAT5, and FXR; hence, fibrate drugs, elevated lipolysis, moderate-protein vegan diets, growth hormone, and bile acids may have potential to increase FGF21 synthesis...
December 19, 2015: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/26683635/selective-novel-inverse-agonists-for-human-gpr43-augment-glp-1-secretion
#19
Bi-Oh Park, Seong Heon Kim, Gye Yeong Kong, Da Hui Kim, Mi So Kwon, Su Ui Lee, Mun-Ock Kim, Sungchan Cho, Sangku Lee, Hyun-Jun Lee, Sang-Bae Han, Young Shin Kwak, Sung Bae Lee, Sunhong Kim
GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A-404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog...
January 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26633898/beneficial-effects-of-evogliptin-a-novel-dipeptidyl-peptidase-4-inhibitor-on-adiposity-with-increased-ppargc1a-in-white-adipose-tissue-in-obese-mice
#20
Yu-Na Chae, Tae-Hyoung Kim, Mi-Kyung Kim, Chang-Yell Shin, Il-Hoon Jung, Yong Sung Sohn, Moon-Ho Son
Although dipeptidyl peptidase 4 (DPP4) is an adipokine known to positively correlate with adiposity, the effects of pharmacological DPP4 inhibition on body composition have not been fully understood. This study was aimed to assess the effects of DPP4 inhibitors on adiposity for the first time in the established obese mice model. The weight loss effects of multiple DPP4 inhibitors were compared after a 4 week treatment in diet-induced obese mice. In addition, a 2 week study was performed to explore and compare the acute effects of evogliptin, a novel DPP4 inhibitor, and exenatide, a glucagon-like peptide-1 (GLP-1) analogue, on whole body composition, energy consumption, various plasma adipokines and gene expression in white adipose tissue (WAT)...
2015: PloS One
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