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GLP-1 AND adipocyte

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Edoardo Mannucci, Ilaria Dicembrini
Until a few years ago, the possibility that glucose-lowering drugs affect glucose metabolism and fracture risk was not even considered. The increased incidence of fractures with thiazolidinediones in women was a causal finding. This phenomenon, which has been demonstrated by large-scale clinical trials, is associated with a reduction in bone density. Thiazolidinediones stimulate adipocyte differentiation, and inhibit osteoblast differentiation, from bone marrow stromal cells; other mechanisms could also be involved in the thiazolidinedione-induced reduction of bone density...
May 2015: Clinical Cases in Mineral and Bone Metabolism
Ahmed M Mostafa, Nadia M Hamdy, Hala O El-Mesallamy, Sherif Z Abdel-Rahman
A promising treatment for obesity involves the use of therapeutic agents that increase the level of the glucagon-like peptide (GLP-1) which reduces appetite and food intake. Native GLP-1 is rapidly metabolized by the dipeptidyl peptidase-4 (DPP-4) enzyme and, as such, GLP-1 mimetics or DPP-4 inhibitors represent promising treatment approaches. Interestingly, obese patient receiving such medications showed improved lipid profiles and cholesterol homeostasis, however the mechanism(s) involved are not known. Members of the ATP-binding cassette (ABC) transporters, including ABCA1 and ABCG1, play essential roles in reverse cholesterol transport and in high density lipoprotein (HDL) formation...
December 25, 2015: Biochemical and Biophysical Research Communications
Masato Furuhashi, Shinya Hiramitsu, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Akina Omori, Megumi Matsumoto, Yuki Watanabe, Kyoko Hoshina, Marenao Tanaka, Norihito Moniwa, Hideaki Yoshida, Junnichi Ishii, Tetsuji Miura
Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 level by therapeutic drugs. Sitagliptin (50 mg/day), a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1), was administered to patients with type 2 diabetes (n = 24) for 12 weeks...
December 2015: Journal of Lipid Research
Hye Min Lee, Bo Sun Joo, Chang Hoon Lee, Heung Yeol Kim, Ji Hoon Ock, Young Seok Lee
OBJECTIVES: Glucagon-like peptide-1 (GLP-1) is an intestinally secreted hormone and it plays an important role in the regulation of glucose homeostasis. However, the possible role of GLP-1 in the differentiation of adipose-derived stem cells (ADSCs) remains unknown. Therefore this study investigated the effect of GLP-1 on the differentiation of ADSCs into osteoblasts and adipocytes. METHODS: ADSCs were isolated from human adipose tissues of the abdomens, cultured and characterized by flow cytometry and multi-lineage potential assay...
August 2015: Journal of Menopausal Medicine
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