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https://www.readbyqxmd.com/read/28202074/exendin-4-in-combination-with-adipose-derived-stem-cells-promotes-angiogenesis-and-improves-diabetic-wound-healing
#1
Eunhui Seo, Jae Soo Lim, Jin-Bum Jun, Woohyuk Choi, In-Sun Hong, Hee-Sook Jun
BACKGROUND: Diminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, is known to have many beneficial effects on diabetes. In addition, mesenchymal stem cells are known to have wound healing effects. We investigated the effects of Ex-4 in combination with human adipose tissue-derived stem cells (ADSCs) on diabetic wound healing in a diabetic animal model...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#2
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28164753/evaluation-of-the-influence-of-the-conjugation-site-of-the-chelator-agent-hynic-to-glp1-antagonist-radiotracer-for-insulinoma-diagnosis
#3
Bluma Linkowski Faintuch, Daniele Seo, Érica Aparecida De Oliveira, Roselaine Campos Targino, Ana Maria Moro
Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium-99m. Two different sites of the biomolecule were selected for chelator attachment. HYNIC-βAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). In conclusion the chelator position in the biomolecule influenced receptor uptake...
January 26, 2017: Current Radiopharmaceuticals
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
#4
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/28134698/68ga-exendin-4-pet-ct-in-evaluation-of-endoscopic-ultrasound-guided-ethanol-ablation-of-an-insulinoma
#5
Yaping Luo, Ji Li, Aiming Yang, Hongbo Yang, Fang Li
A 32-year-old man with endogenous hyperinsulinemic hypoglycemia was clinically diagnosed with an insulinoma. Conventional imaging result was negative, and a previous exploratory laparotomy with distal pancreatectomy failed to detect the tumor. Ga-exendin-4 PET/CT showed a lesion with intense radioactivity in the head of the pancreas suggestive of an insulinoma, and endoscopic ultrasound-guided ethanol ablation was performed. Postablation evaluation with Ga-exendin-4 PET/CT showed markedly decreased radioactivity of the tumor...
January 27, 2017: Clinical Nuclear Medicine
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/28117023/an-overview-of-bioactive-peptides-for-in-vivo-imaging-and-therapy-in-human-diseases
#7
Anna Lucia Tornesello, Maria Lina Tornesello, Franco M Buonaguro
Radiolabeled peptides, designed to bind with high affinity receptors selectively expressed on cell membranes of different human tissues, represent valuable tools for in vivo imaging of several human diseases. Solid-phase peptide synthesis as well as availability of bifunctional chelating agents and prosthetic groups allows the production and radiolabeling of several peptide-based molecules which are useful to target specific receptors on different cancer types. Among them, octreotide and other analogues of somatostatin, vasoactive intestinal peptide, CCK analogues, bombesin, α-MSH analogues, neurotensin, exendin, RGD substance P, conjugated to appropriate chelators, such as DTPA, NOTA, DOTA or TETA, and radiolabeled with specific radionuclides, have already been translated into the clinical practice with remarkable sensitivity and diagnostic accurateness...
January 20, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28106207/natural-sweetener-agave-inhibits-gastric-emptying-in-rats-by-a-cholecystokinin-2-and-glucagon-like-peptide-1-receptor-dependent-mechanism
#8
E Bihter Gürler, Dilek Özbeyli, Hülya Buzcu, Sezin Bayraktar, İrem Carus, Beyza Dağ, Yasemin Geriş, Seda Jeral, Berrak Ç Yeğen
Low-calorie sweeteners are considered to be beneficial in calorie control, but the impact of these sweeteners on gastric emptying is not well described. The purpose of this study was to compare the gastric emptying rate of agave nectar with those of glucose and fructose, and to evaluate the interaction of cholecystokinin (CCK)-1, CCK-2 and glucagon-like peptide-1 (GLP-1) receptors in agave-induced alterations in gastric emptying. Female Sprague-Dawley rats were fitted with gastric cannulas. Following the recovery, the gastric emptying rates of glucose, fructose and agave at 12...
January 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#9
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103022/discovery-of-a-novel-series-of-orally-bioavailable-and-cns-penetrant-glucagon-like-peptide-1-receptor-glp-1r-non-competitive-antagonists-based-on-a-1-3-disubstituted-7-aryl-5-5-bis-trifluoromethyl-5-8-dihydropyrimido-4-5-d-pyrimidine-2-4-1h-3h-dione-core
#10
Kellie D Nance, Emily L Days, C David Weaver, Anastasia Coldren, Tiffany D Farmer, Hyekyung P Cho, Colleen M Niswender, Anna L Blobaum, Kevin D Niswender, Craig W Lindsley
A duplexed, functional multi-addition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) non-competitive antagonist. Antagonist 5d not only blocked Exendin-4-stimulated insulin release in islets, but also lowered insulin levels while increasing blood glucose in vivo.
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28098360/morroniside-a-secoiridoid-glycoside-from-cornus-officinalis-attenuates-neuropathic-pain-by-activation-of-spinal-glucagon-like-peptide-1-receptors
#11
Meng Xu, Hai-Yun Wu, Hao Liu, Nian Gong, Yi-Rui Wang, Yong-Xiang Wang
BACKGROUND AND PURPOSE: Iridoid glycosides with intact double bond scaffold of cyclopentapyran were reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and possess antinociception and neuroprotection. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid replaced by a six-membered cyclic inner ether fragment. This study investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had antihypersensitivity activities in neuropathy...
January 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-epidermal-growth-factor-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#12
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a three-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28089587/development-of-111-in-labeled-exendin-9-39-derivatives-for-single-photon-emission-computed-tomography-imaging-of-insulinoma
#13
Hiroyuki Kimura, Hirokazu Matsuda, Yu Ogawa, Hiroyuki Fujimoto, Kentaro Toyoda, Naotaka Fujita, Kenji Arimitsu, Keita Hamamatsu, Yusuke Yagi, Masahiro Ono, Nobuya Inagaki, Hideo Saji
Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Accordingly, radiolabeled exendin(9-39) derivatives have also been investigated as insulinoma imaging probes that might be less likely to induce hypoglycemia...
January 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28088959/-effect-of-exendin-4-on-lipid-deposition-in-skeletal-muscle-of-diet-induced-obese-mice-and-its-underlying-mechanism
#14
H Y Cao, F Xu, Z L Chen, B S Lin, X B Zheng, S H Yuan, H Liang, J P Weng
Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg(-1)·d(-1) exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28067253/whole-organ-and-islet-of-langerhans-dosimetry-for-calculation-of-absorbed-doses-resulting-from-imaging-with-radiolabeled-exendin
#15
Inge van der Kroon, Wietske Woliner-van der Weg, Maarten Brom, Lieke Joosten, Cathelijne Frielink, Mark W Konijnenberg, Eric P Visser, Martin Gotthardt
Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#16
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28043300/-influences-of-exendin-4-on-the-secretion-function-of-islet-beta-cells-from-rats-in-the-early-stage-of-severe-scald
#17
D X Zhao, L Ma, Z A Shen, D W Li, Y R Shang, K Yin, W F Cheng, X Wang, Z X Liu
Objective: To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods: Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water...
December 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#18
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27993221/exendin-4-a-glucagon-like-peptide-1-analogue-accelerates-diabetic-wound-healing
#19
Jun-Neng Roan, Han-Ni Cheng, Chao-Chung Young, Chi-Ju Lee, Ming-Long Yeh, Chwan-Yau Luo, Yau-Sheng Tsai, Chen-Fuh Lam
BACKGROUND: Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. MATERIALS AND METHODS: Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27975209/critical-role-for-glp-1-in-symptomatic-post-bariatric-hypoglycaemia
#20
Colleen M Craig, Li-Fen Liu, Carolyn F Deacon, Jens J Holst, Tracey L McLaughlin
AIMS/HYPOTHESIS: Post-bariatric hypoglycaemia (PBH) is a rare, but severe, metabolic disorder arising months to years after bariatric surgery. It is characterised by symptomatic postprandial hypoglycaemia, with inappropriately elevated insulin concentrations. The relative contribution of exaggerated incretin hormone signalling to dysregulated insulin secretion and symptomatic hypoglycaemia is a subject of ongoing inquiry. This study was designed to test the hypothesis that PBH and associated symptoms are primarily mediated by glucagon-like peptide-1 (GLP-1)...
March 2017: Diabetologia
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