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https://www.readbyqxmd.com/read/28938428/glp-1-receptor-activation-inhibits-palmitate-induced-apoptosis-via-ceramide-in-human-cardiac-progenitor-cells
#1
Anna Leonardini, Rossella D'Oria, Maria Angela Incalza, Cristina Caccioppoli, Valentina Andrulli Buccheri, Angelo Cignarelli, Domenico Paparella, Vito Margari, Annalisa Natalicchio, Sebastio Perrini, Francesco Giorgino, Luigi Laviola
Context: Increased apoptosis of cardiomyocytes and cardiac progenitor cells (CPCs) in response to saturated fatty acids (SFA) can lead to myocardial damage and dysfunction. Ceramides mediate lipotoxicity-induced apoptosis. GLP-1 receptor (GLP1R) agonists exert beneficial effects on cardiac cells in experimental models. Objective: To investigate the protective effects of GLP1R activation on SFA-mediated apoptotic death of human CPCs. Design: Human CPCs were isolated from cardiac appendages of non-diabetic donors and then exposed to palmitate with or without pre-treatment with the GLP1R agonist exendin-4...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#2
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28774890/mir-338-controls-bpa-triggered-pancreatic-islets-insulin-secretory-dysfunction-from-compensation-to-decompensation-by-targeting-pdx-1
#3
Jie Wei, Dongxiao Ding, Tao Wang, Qiong Liu, Yi Lin
Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/day) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice...
August 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28702330/neonatal-glp1r-activation-limits-adult-adiposity-by-durably-altering-hypothalamic-architecture
#4
Andrea V Rozo, Daniella A Babu, PoMan A Suen, David N Groff, Randy J Seeley, Rebecca A Simmons, Patrick Seale, Rexford S Ahima, Doris A Stoffers
OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28702324/the-endogenous-preproglucagon-system-is-not-essential-for-gut-growth-homeostasis-in-mice
#5
Pernille Wismann, Pernille Barkholt, Thomas Secher, Niels Vrang, Henrik B Hansen, Palle Bekker Jeppesen, Laurie L Baggio, Jacqueline A Koehler, Daniel J Drucker, Darleen A Sandoval, Jacob Jelsing
OBJECTIVE: The prevalence of obesity and related co-morbidities is reaching pandemic proportions. Today, the most effective obesity treatments are glucagon-like peptide 1 (GLP-1) analogs and bariatric surgery. Interestingly, both intervention paradigms have been associated with adaptive growth responses in the gut; however, intestinotrophic mechanisms associated with or secondary to medical or surgical obesity therapies are poorly understood. Therefore, the objective of this study was to assess the local basal endogenous and pharmacological intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28609478/purification-of-family-b-g-protein-coupled-receptors-using-nanodiscs-application-to-human-glucagon-like-peptide-1-receptor
#6
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/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#7
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377501/the-transcription-factor-pax6-is-required-for-pancreatic-%C3%AE-cell-identity-glucose-regulated-atp-synthesis-and-ca-2-dynamics-in-adult-mice
#8
Ryan K Mitchell, Marie-Sophie Nguyen-Tu, Pauline Chabosseau, Rebecca M Callingham, Timothy J Pullen, Rebecca Cheung, Isabelle Leclerc, David J Hodson, Guy A Rutter
Heterozygous mutations in the human paired box gene PAX6 lead to impaired glucose tolerance. Although embryonic deletion of the Pax6 gene in mice leads to loss of most pancreatic islet cell types, the functional consequences of Pax6 loss in adults are poorly defined. Here we developed a mouse line in which Pax6 was selectively inactivated in β cells by crossing animals with floxed Pax6 alleles to mice expressing the inducible Pdx1CreERT transgene. Pax6 deficiency, achieved by tamoxifen injection, caused progressive hyperglycemia...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28368384/glp-1-acts-on-habenular-avoidance-circuits-to-control-nicotine-intake
#9
Luis M Tuesta, Zuxin Chen, Alexander Duncan, Christie D Fowler, Masago Ishikawa, Brian R Lee, Xin-An Liu, Qun Lu, Michael Cameron, Matthew R Hayes, Theodore M Kamenecka, Matthew Pletcher, Paul J Kenny
Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28270438/menin-and-prmt5-suppress-glp1-receptor-transcript-and-pka-mediated-phosphorylation-of-foxo1-and-creb
#10
Abdul Bari Muhammad, Bowen Xing, Chengyang Liu, Ali Naji, Xiaosong Ma, Rebecca A Simmons, Xianxin Hua
Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic β-cell proliferation. Tamoxifen-inducible deletion of multiple endocrine neoplasia type 1 (MEN1) gene, which encodes the protein menin, increases β-cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of β-cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28144621/glp-1r-signaling-directly-activates-arcuate-nucleus-kisspeptin-action-in-brain-slices-but-does-not-rescue-luteinizing-hormone-inhibition-in-ovariectomized-mice-during-negative-energy-balance
#11
Kristy M Heppner, Arian F Baquero, Camdin M Bennett, Sarah R Lindsley, Melissa A Kirigiti, Baylin Bennett, Martha A Bosch, Aaron J Mercer, Oline K Rønnekleiv, Cadence True, Kevin L Grove, M Susan Smith
Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#12
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
April 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28053040/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#13
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27917862/purslane-portulaca-oleracea-seed-consumption-and-aerobic-training-improves-biomarkers-associated-with-atherosclerosis-in-women-with-type-2-diabetes-t2d
#14
Firouzeh Dehghan, Rahman Soori, Khadijeh Gholami, Mitra Abolmaesoomi, Ashril Yusof, Sekaran Muniandy, Sara Heidarzadeh, Parvin Farzanegi, Mohammad Ali Azarbayjani
The aim of this study was to investigate the responses of atherosclerosis plaque biomarkers to purslane seed consumption and aerobic training in women with T2D. 196 women with T2D were assigned into; (1) placebo (PL), (2) aerobic training+placebo (AT + PL), 3) purslane seeds (PS), aerobic training+purslane seeds (AT + PS). The training program and purslane seeds consumption (2.5 g lunch and 5 g dinner) were carried out for 16 weeks. The components of purslane seed were identified and quantified by GC-MS...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908915/the-hypothalamic-glucagon-like-peptide-1-receptor-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#15
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
February 2017: Diabetes
https://www.readbyqxmd.com/read/27858848/a-genetic-variant-in-glp1r-is-associated-with-response-to-dpp-4-inhibitors-in-patients-with-type-2-diabetes
#16
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-Ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27810935/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#17
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1) mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1 (Sim1), a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with Sim1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal (HPA) axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27677765/metabolic-effects-of-orally-administered-small-molecule-agonists-of-gpr55-and-gpr119-in-multiple-low-dose-streptozotocin-induced-diabetic-and-incretin-receptor-knockout-mice
#18
Aine M McKillop, Brian M Moran, Yasser H A Abdel-Wahab, Noella M Gormley, Peter R Flatt
AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0...
December 2016: Diabetologia
https://www.readbyqxmd.com/read/27624071/aurora-kinase-a-overexpression-in-mouse-mammary-epithelium-induces-mammary-adenocarcinomas-harboring-genetic-alterations-shared-with-human-breast-cancer
#19
Warapen Treekitkarnmongkol, Hiroshi Katayama, Kazuharu Kai, Kaori Sasai, Jennifer Carter Jones, Jing Wang, Li Shen, Aysegul A Sahin, Mihai Gagea, Naoto T Ueno, Chad J Creighton, Subrata Sen
Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition...
December 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27475229/stromal-cell-derived-factor-1-is-upregulated-by%C3%A2-dipeptidyl-peptidase-4-inhibition-and-has%C3%A2-protective-roles-in-progressive-diabetic%C3%A2-nephropathy
#20
Satoru Takashima, Hiroki Fujita, Hiromi Fujishima, Tatsunori Shimizu, Takehiro Sato, Tsukasa Morii, Katsushi Tsukiyama, Takuma Narita, Takamune Takahashi, Daniel J Drucker, Yutaka Seino, Yuichiro Yamada
The role of stromal cell-derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice...
October 2016: Kidney International
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