keyword
https://read.qxmd.com/read/38477664/the-prostaglandin-e-2-ep3-receptor-has-disparate-effects-on-islet-insulin-secretion-and-content-in-%C3%AE-cells-in-a-high-fat-diet-induced-mouse-model-of-obesity
#1
JOURNAL ARTICLE
Joshua C Neuman, Austin Reuter, Kathryn A Carbajal, Michael D Schaid, Grant Kelly, Kelsey Connors, Cecilia Kaiser, Joshua Krause, Liam D Hurley, Angela Olvera, Dawn Belt Davis, Jaclyn A Wisinski, Maureen Gannon, Michelle E Kimple
Signaling through Prostaglandin E2 EP3 receptor (EP3) actively contributes to the β-cell dysfunction of type 2 diabetes (T2D). In T2D models, full-body EP3 knockout mice have a significantly worse metabolic phenotype than wild-type controls due to hyperphagia and severe insulin resistance resulting from loss of EP3 in extra-pancreatic tissues, masking any potential beneficial effects of EP3 loss in the β-cell. We hypothesized β-cell-specific EP3 knockout (EP3 βKO) mice would be protected from high-fat diet (HFD)-induced glucose intolerance, phenocopying mice lacking the EP3 effector, Gɑz , which is much more limited in its tissue distribution...
March 13, 2024: American Journal of Physiology. Endocrinology and Metabolism
https://read.qxmd.com/read/38471465/heterogeneity-of-multiple-pancreatic-neuroendocrine-tumors-identified-by-68ga-dotanoc-and-68ga-exendin-4-pet-ct-in-a-patient-with-endogenous-hyperinsulinemic-hypoglycemia-and-multiple-endocrine-neoplasia-1
#2
Junyan Xu, Xiaoping Xu, Meng Zhang, Wensheng Liu, Jie Chen, Shaoli Song
Insulinomas are the most frequent functional neuroendocrine tumors of pancreas. In about 10% cases, insulinomas are associated with hereditary syndrome including multiple endocrine neoplasia 1 (MEN1). Herein, we presented a case of 44-year-old female with recurrent hypoglycemia. In December 1998, this patient has undergone resection of two pancreatic lesions due to hypoglycemia and diagnosed as insulinoma. After operation, the symptom of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently and even coma...
March 12, 2024: Neuroendocrinology
https://read.qxmd.com/read/38471012/gut-microbiota-tryptophan-metabolism-glp-1-axis-participates-in-%C3%AE-cell-regeneration-induced-by-dapagliflozin
#3
JOURNAL ARTICLE
Yafei Jiang, Jin Yang, Li Xia, Tianjiao Wei, Xiaona Cui, Dandan Wang, Zirun Jin, Xiafang Lin, Fei Li, Kun Yang, Shan Lang, Ye Liu, Jing Hang, Zhe Zhang, Tianpei Hong, Rui Wei
Sodium-glucose co-transporter 2 (SGLT2) inhibitor, an efficacious anti-diabetic agent, which has cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multi-omics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice...
March 12, 2024: Diabetes
https://read.qxmd.com/read/38432328/functional-maturation-and-longitudinal-imaging-of-intraportal-neonatal-porcine-islet-grafts-in-genetically-diabetic-pigs
#4
JOURNAL ARTICLE
Johanna Pilz, Nicol Gloddek, Felix Lindheimer, Magdalena J Lindner, Daniel Puhr-Westerheide, Muzzafer Ümütlü, Clemens Cyran, Max Seidensticker, Richard Lindner, Martin Kraetzl, Simone Renner, Daphne Merkus, Daniel Teupser, Peter Bartenstein, Sibylle I Ziegler, Eckhard Wolf, Elisabeth Kemter
Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes (T1D). However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, non-invasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68 Ga]Ga-DOTA-Exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs...
March 1, 2024: American Journal of Transplantation
https://read.qxmd.com/read/38403256/targeting-autophagy-to-counteract-neuroinflammation-a-novel-antidepressant-strategy
#5
REVIEW
Hua Gan, Qingyu Ma, Wenzhi Hao, Nating Yang, Zhe-Sheng Chen, Lijuan Deng, Jiaxu Chen
Depression is a common disease that affects physical and mental health and imposes a considerable burden on afflicted individuals and their families worldwide. Depression is associated with a high rate of disability and suicide. It causes a severe decline in productivity and quality of life. Unfortunately, the pathophysiological mechanisms underlying depression have not been fully elucidated, and the risk of its treatment is still presented. Studies have shown that the expression of autophagic markers in the brain and peripheral inflammatory mediators are dysregulated in depression...
February 23, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/38395386/human-gestational-diabetes-mellitus-derived-exosomes-impair-glucose-homeostasis-in-pregnant-mice-and-stimulate-functional-maturation-of-offspring-islets
#6
JOURNAL ARTICLE
Linhai Zou, Chunxue Xu, Li Wang, Xiangju Cao, Xinyu Jia, Zhihong Yang, Guohui Jiang, Lixia Ji
AIMS: Pancreatic islets undergo critical development and functional maturation during the perinatal period when they are highly sensitive to microenvironment. We aim to determine the effects and mechanisms of gestational diabetes mellitus (GDM) hypermetabolic stress on glucose homeostasis in pregnant mice and functional maturation of the islets of their offspring. MAIN METHODS: Exosomes were extracted from the umbilical vein blood of individuals with or without GDM for administration to pregnant mice...
February 21, 2024: Life Sciences
https://read.qxmd.com/read/38360293/distinct-roles-of-the-extracellular-surface-residues-of-glucagon-like-peptide-1-receptor-in-%C3%AE-arrestin-1-2-signaling
#7
JOURNAL ARTICLE
Saifei Lei, Qian Meng, Yanyun Liu, Qiaofeng Liu, Antao Dai, Xiaoqing Cai, Ming-Wei Wang, Qingtong Zhou, Hu Zhou, Dehua Yang
Glucagon-like peptide-1 receptor (GLP-1R) is a prime drug target for type 2 diabetes and obesity. The ligand initiated GLP-1R interaction with G protein has been well studied, but not with β-arrestin 1/2. Therefore, bioluminescence resonance energy transfer (BRET), mutagenesis and an operational model were used to evaluate the roles of 85 extracellular surface residues on GLP-1R in β-arrestin 1/2 recruitment triggered by three representative GLP-1R agonists (GLP-1, exendin-4 and oxyntomodulin). Residues selectively regulated β-arrestin 1/2 recruitment for diverse ligands, and β-arrestin isoforms were identified...
February 13, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38354757/glp-1-receptor-agonist-attenuates-tubular-cell-ferroptosis-in-diabetes-via-enhancing-ampk-fatty-acid-metabolism-pathway-through-macropinocytosis
#8
JOURNAL ARTICLE
Rui Shen, Songyan Qin, Yunhui Lv, Dandan Liu, Qingqing Ke, Caifeng Shi, Lei Jiang, Junwei Yang, Yang Zhou
Kidney tubules are mostly responsible for pathogenesis of diabetic kidney disease. Actively reabsorption of iron, high rate of lipid metabolism and exposure to concentrated redox-active compounds constructed the three main pillars of ferroptosis in tubular cells. However, limited evidence has indicated that ferroptosis is indispensable for diabetic tubular injury. Glucagon-like peptide-1 receptor agonist (GLP-1RA) processed strong benefits on kidney outcomes in people with diabetes. Moreover, GLP-1RA may have additive effects by improving dysmetabolism besides glucose control and weight loss...
February 12, 2024: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/38337597/dipeptidyl-peptidase-4-and-glucagon-like-peptide-1-a-link-in-the-connection-between-periodontitis-and-diabetes-mellitus-what-do-we-know-so-far-a-scoping-review
#9
REVIEW
Theodora Claudia Gheonea, Petra Șurlin, Flavia Mirela Nicolae, Dorin Nicolae Gheorghe, Dora Maria Popescu, Ion Rogoveanu
Periodontitis is a common condition affecting the tissues surrounding and supporting teeth. In addition to oral health concerns, periodontal disease increases the chance of developing systemic illnesses including type 2 diabetes mellitus. Porphyromonas gingivalis, a key-stone pathogen that has been linked to the pathophysiology of periodontal disease, can generate a series of dipeptide producing exopeptidases, dipeptidyl peptidases (DPP). DPP-4 levels in gingival crevicular fluid have been shown to increase during active periodontal disease, which may lead to their association with the disease's progression...
February 4, 2024: Journal of Clinical Medicine
https://read.qxmd.com/read/38331374/the-estrogenic-reduction-in-water-intake-stimulated-by-dehydration-involves-estrogen-receptor-alpha-and-a-potential-role-for-glp-1
#10
JOURNAL ARTICLE
Julia A Howell, Andrea A Edwards, Jessica Santollo
It is well documented that estrogens inhibit fluid intake. Most of this research, however, has focused on fluid intake in response to dipsogenic hormone and/or drug treatments in euhydrated rats. Additional research is needed to fully characterize the fluid intake effects of estradiol in response to true hypovolemia. As such, the goals of this series of experiments were to provide a detailed analysis of water intake in response to water deprivation in ovariectomized female rats treated with estradiol. In addition, these experiments also tested if activation of estrogen receptor alpha is sufficient to reduce water intake stimulated by water deprivation and tested for a role of glucagon like peptide-1 in the estrogenic control of water intake...
February 6, 2024: Physiology & Behavior
https://read.qxmd.com/read/38313829/the-glp-1-receptor-is-expressed-in-vivo-by-human-metastatic-prostate-cancer
#11
JOURNAL ARTICLE
Mark S Stein, Victor Kalff, Scott G Williams, Declan G Murphy, Peter G Colman, Michael S Hofman
OBJECTIVES: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro . Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo ...
January 1, 2024: Endocr Oncol
https://read.qxmd.com/read/38300808/glp-1-and-pyy-for-the-treatment-of-obesity-use-of-agonists-and-antagonists-in-diet-induced-rats-a-pilot-study
#12
JOURNAL ARTICLE
Marie Oertel, Christian G Ziegler, Michael Kohlhaas, Alexander Nickel, Simon Kloock, Christoph Maack, Vasco Sequeira, Martin Fassnacht, Ulrich Dischinger
OBJECTIVE: Combination therapies with gut hormone analogues represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin(9-39)), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogues (PYY3-36/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ 31020028)...
February 1, 2024: Endocrine Connections
https://read.qxmd.com/read/38287130/safety-tolerability-pharmacokinetic-pharmacodynamic-and-immunogenicity-profiles-of-exendin-4-igg4-fc-in-healthy-subjects-a-phase-1-single-centre-randomized-double-blind-dose-escalation-study
#13
JOURNAL ARTICLE
Gui-Ling Chen, Yang Liu, Xue-Feng Gao, Kai-Qi Wu, Yun-Kai Yang, Yong Chen, Cong-Gao Peng, Ting-Han Jin, Yu-Bao Huang, Yao-Wen Zhang, Jing Su, Qi Jiang, Tong Guo, Jie Zhao, Xiang-Nan Peng, Jing-Yu Peng, Si-Xiu Li, Yong-Li Sun, Hong-Mei Zhang, Yan-Li Fu, Dan Luo, Yaru Ma, Zhen-Wei Shen, Yun-Tao Zhang, Zhang-Fei Shou
AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0...
January 29, 2024: Diabetes, Obesity & Metabolism
https://read.qxmd.com/read/38280449/renal-tubule-specific-atgl-deletion-links-kidney-lipid-metabolism-to-glucagon-like-peptide-1-and-insulin-secretion-independent-of-renal-inflammation-or-lipotoxicity
#14
JOURNAL ARTICLE
Maria F Fernandes, Juan J Aristizabal-Henao, Phillip M Marvyn, Iman M'Hiri, Meghan A Wiens, Monica Hoang, Manuel Sebastian, Renato Nachbar, Philippe St-Pierre, Kalsha Diaguarachchige DeSilva, Geoffrey A Wood, Jamie W Joseph, Christine A Doucette, André Marette, Ken D Stark, Robin E Duncan
OBJECTIVE: Lipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health. METHODS: Male and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10-12 and 16-18 weeks of age...
January 25, 2024: Molecular Metabolism
https://read.qxmd.com/read/38269495/glp1r-boosts-survival-migration-and-invasion-of-endometrial-cancer-cells-and-protects-against-ferroptotic-cell-death
#15
JOURNAL ARTICLE
Wu Li, Wen Lyu, Songjun Liu, Fan Ruan, Xinmei Zhang
BACKGROUND: Despite the strong evidence concerning carcinogenic roles of glucagon-like peptide 1 receptor (GLP1R), the role of this gene in endometrial cancer (EC) remains elusive. This study investigated the properties of GLP1R on EC in vitro . METHODS: The expression of GLP1R in EC was detected by RT-qPCR, immunohistochemistry, and western blotting. Cell viability, cell cycle, apoptosis, migration, invasion and ferroptosis were assessed through CCK-8, flow cytometry, wound healing, transwell, DCFH-DA and western blotting, respectively...
December 2024: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://read.qxmd.com/read/38241936/introduction-of-a-fatty-acid-chain-modification-to-prolong-circulatory-half-life-of-a-radioligand-towards-glucose-dependent-insulinotropic-polypeptide-receptor
#16
JOURNAL ARTICLE
Amina Khalil, Sona Hakhverdyan, Pierre Cheung, Martin Bossart, Michael Wagner, Olof Eriksson, Irina Velikyan
BACKGROUND: The beneficial role of glucose-dependent insulinotropic polypeptide receptor (GIPR) in weight control and maintaining glucose levels has led to the development of several multi-agonistic peptide drug candidates, targeting GIPR and glucagon like peptide 1 receptor (GLP1R) and/or the glucagon receptor (GCGR). The in vivo quantification of target occupancy by these drugs would accelerate the development of new drug candidates. The aim of this study was to evaluate a novel peptide (GIP1234), based on previously reported ligand DOTA-GIP-C803, modified with a fatty acid moiety to prolong its blood circulation...
January 10, 2024: Nuclear Medicine and Biology
https://read.qxmd.com/read/38230775/exendin-4-a-potential-therapeutic-strategy-for-alzheimer-s-disease-and-parkinson-s-disease
#17
REVIEW
Aanchal Verma, Shobhit Chaudhary, Kunal Solanki, Ahsas Goyal, Harlokesh Narayan Yadav
Neurodegenerative disorders, which affect millions worldwide, are marked by a steady decline of neurons that are selectively susceptible. Due to the complex pathological processes underlying neurodegeneration, at present, there is no viable therapy available for neurodegenerative disorders. Consequently, the establishment of a novel therapeutic approach for such conditions is a clinical void that remains. The potential significance of various peptides as neuroprotective interventions for neurodegenerative disorders is gaining increasing attention...
January 2024: Chemical Biology & Drug Design
https://read.qxmd.com/read/38224039/intramuscular-injection-of-palmitic-acid-conjugated-exendin-4-loaded-multivesicular-liposomes-for-long-acting-and-improving-in-situ-stability
#18
JOURNAL ARTICLE
Huixian Tian, Minsi Chang, Yanlin Lyu, Nan Dong, Nini Yu, Tian Yin, Yu Zhang, Haibing He, Jingxin Gou, Xing Tang
BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the E×4formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified E×4(Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process...
January 15, 2024: Expert Opinion on Drug Delivery
https://read.qxmd.com/read/38196815/insulinoma-metastatic-recurrence-38-years-following-initial-diagnosis-in-pregnancy
#19
Christopher A Preston, Nirupa Sachithanandan, Ie-Wen Sim, Jon van Heerden, Stephen Farrell
A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography...
February 2024: JCEM Case Rep
https://read.qxmd.com/read/38186959/enhanced-bone-regeneration-via-endochondral-ossification-using-exendin-4-modified-mesenchymal-stem-cells
#20
JOURNAL ARTICLE
Zihao He, Hui Li, Yuanyuan Zhang, Shuang Gao, Kaini Liang, Yiqi Su, Yanan Du, Du Wang, Dan Xing, Zhen Yang, Jianhao Lin
Nonunions and delayed unions pose significant challenges in orthopedic treatment, with current therapies often proving inadequate. Bone tissue engineering (BTE), particularly through endochondral ossification (ECO), emerges as a promising strategy for addressing critical bone defects. This study introduces mesenchymal stem cells overexpressing Exendin-4 (MSC-E4), designed to modulate bone remodeling via their autocrine and paracrine functions. We established a type I collagen (Col-I) sponge-based in vitro model that effectively recapitulates the ECO pathway...
April 2024: Bioactive Materials
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