Article
Biochemistry & Molecular Biology
Long Teng, Tuchen Guan, Beibei Guo, Chao Ma, Ge Lin, Ronghua Wu, Man Xu, Mei Liu, Yan Liu
Summary: This study established an in vitro model to screen for genes involved in neurite outgrowth, and found that the GIP-GIPR axis can promote axonal outgrowth; the results showed that GIP significantly improved extension of axon.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Endocrinology & Metabolism
Gemma Pujadas, Laurie L. Baggio, Kiran Deep Kaur, Brent A. McLean, Xiemin Cao, Daniel J. Drucker
Summary: The loss of GIPR signaling in mice leads to increased aortic atherosclerosis and enhanced inflammation in the aorta and liver, despite reduced weight gain and preserved glucose homeostasis. These findings indicate that GIPR has a broader role in suppressing inflammation-related pathophysiology beyond its classical incretin role in metabolic control.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Florent X. Smit, Wijnand J. C. van der Velden, Husun S. Kizilkaya, Amalie Norskov, Michael Luckmann, Tobias N. Hansen, Alexander H. Sparre-Ulrich, Katrine Qvotrup, Thomas M. Frimurer, Mette M. Rosenkilde
Summary: The study investigates the structure and function of the GIP receptor (GIPR) and identifies key residues involved in ligand binding and receptor activation. The findings suggest that disrupting a specific salt bridge by GIPR antagonists can significantly reduce GIPR activation, providing insights for rational ligand design targeting the GIPR.
Article
Endocrinology & Metabolism
Jonathan E. Campbell, Jacqueline L. Beaudry, Berit Svendsen, Laurie L. Baggio, Andrew N. Gordon, John R. Ussher, Chi Kin Wong, Fiona M. Gribble, David A. D'Alessio, Frank Reimann, Daniel J. Drucker
Summary: This study reveals that GIP receptors are predominantly expressed in pericytes and mesothelial cells, rather than adipocytes, in white adipose tissue. This finding has mechanistic implications for understanding the role of GIP and GIP-based co-agonists in controlling adipose tissue biology.
Article
Endocrinology & Metabolism
Xin-shang Wang, Yong-li Jiang, Liang Lu, Ban Feng, Xue Ma, Kun Zhang, Shao-yu Guan, Le Yang, Qing-yu Fan, Xiao-chen Zhu, Fan Yang, Jing-yu Qi, Liu-kun Yang, Xu-bo Li, Ming-gao Zhao, Wen Jiang, Zhen Tian, Shui-bing Liu
Summary: Chronic pain, often accompanied by anxiety disorders, is difficult to treat due to the exacerbating relationship between the two conditions. GIP, previously studied in neurodegenerative diseases, was found to have analgesic and anxiolytic effects in the treatment of chronic inflammatory pain and pain-related anxiety, possibly through attenuation of neuroinflammation and inhibition of excitatory transmission in the ACC. GIPR activation may be a promising target for future therapies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Irina Efimova, Inbar Steinberg, Isabel Zvibel, Anat Neumann, Dana Fernanda Mantelmacher, Daniel J. Drucker, Sigal Fishman, Chen Varol
Summary: GIPR plays a significant role in supporting WAT type 2 immunity in myeloid immune cells, and its deficiency affects the type 2 immune networks, particularly in adipose tissue.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Elita Yuliantie, Wijnand J. C. van der Velden, Viktorija Labroska, Antao Dai, Fenghui Zhao, Sanaz Darbalaei, Giuseppe Deganutti, Tongyang Xu, Qingtong Zhou, Dehua Yang, Mette M. Rosenkilde, Patrick M. Sexton, Ming-Wei Wang, Denise Wootten
Summary: This study investigated the structure-function relationship of GIPR, revealing two critical interaction networks that affect cAMP accumulation and recruitment of beta-arrestin 2. The activation of ERK1/2 was found to be largely independent of other signaling pathways, indicating distinct signaling properties.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Cell Biology
Nadya M. Morrow, Antonio A. Hanson, Erin E. Mulvihill
Summary: Enteroendocrine cells play a crucial role in regulating nutrient intake and disposal through the production and secretion of peptides. Understanding the identity of cells expressing Glp1r, Glp2r, and Gipr in different models can provide insights into dysregulation seen in obesity and diabetes. Further research on G-protein coupled receptor circuits in the intestine and their alterations with high-fat diet feeding is also important in understanding metabolic diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Miranda Rogers, Dipender Gill, Emma Ahlqvist, Tim Robinson, Daniela Mariosa, Mattias Johansson, Ricardo Cortez Cardoso Penha, Laure Dossus, Marc J. Gunter, Victor Moreno, George Davey Smith, Richard M. Martin, James Yarmolinsky
Summary: Preclinical and genetic studies show that impaired GIPR signaling increases glycemic control difficulties and its relationship with cancer risk influenced by impaired glucose homeostasis is unclear. This study examines a variant in GIPR, rs1800437 (E354Q), which impairs long-term GIPR signaling, and its association with the risk of 6 cancers influenced by impaired glucose homeostasis. The results suggest that the E354Q variant is associated with higher risk of breast cancer and has adverse effects on glucose concentrations, insulin secretion, and testosterone concentrations.
Article
Biochemistry & Molecular Biology
Mattia Dalle Nogare, Sarah D'Annunzio, Giovanni Vazza, Daniela Regazzo, Luna Picello, Luca Denaro, Giacomo Voltan, Carla Scaroni, Filippo Ceccato, Gianluca Occhi
Summary: It has been found that aberrant expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in GH-secreting pituitary adenomas (GH-PAs) can lead to an increase in GH levels after glucose load. This study aimed to investigate if DNA methylation changes in the GIPR locus could contribute to this phenomenon. The results showed differences in methylation levels between GIPR-positive and GIPR-negative GH-PAs, indicating that epigenetic regulation affects GIPR expression. Treatment with 5-aza-2'-deoxycytidine resulted in a reduction in Gipr expression, suggesting a correlation between DNA methylation and Gipr expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Simona Daniele, Simona Saporiti, Stefano Capaldi, Deborah Pietrobono, Lara Russo, Uliano Guerrini, Tommaso Laurenzi, Elham Ataie Kachoie, Luca Palazzolo, Vincenzo Russo, Maria Pia Abbracchio, Ivano Eberini, Maria Letizia Trincavelli
Summary: GPR17, a key regulator of myelination, is activated by endogenous ligands and pro-inflammatory molecules. This study investigates the structural and functional interactions between GPR17 and chemokine receptors CXCR2 and CXCR4. The results show that these receptors can form heterodimers and modulate intracellular cAMP levels. This cross-talk between receptors could impact the neuroinflammatory environment associated with demyelinating events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Xiaorui Lyu, Kemin Yan, WenJing Hu, Hanyuan Xu, Xiaonan Guo, Zhibo Zhou, Huijuan Zhu, Hui Pan, Linjie Wang, Hongbo Yang, Fengying Gong
Summary: In this study, the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) were investigated for the first time. The results showed that intragastric SY/HSYA notably decreased serum GIP levels and GIP staining in diet-induced obese (DIO) mice, and also suppressed GIPR signaling in both the hypothalamus and subcutaneous white adipose tissue. Furthermore, intragastric SY/HSYA reduced food intake and body weight gain, as well as decreased serum leptin levels in DIO mice.
PHYTOTHERAPY RESEARCH
(2023)
Article
Endocrinology & Metabolism
Kimberley El, Jonathan D. Douros, Francis S. Willard, Aaron Novikoff, Ashot Sargsyan, Diego Perez-Tilve, David B. Wainscott, Bin Yang, Alex Chen, Donald Wothe, Callum Coupland, Mattias H. Tschoep, Brian Finan, David A. D'Alessio, Kyle W. Sloop, Timo D. Mueller, Jonathan E. Campbell
Summary: This study shows that tirzepatide, through dual activation of GLP-1R and GIPR, is highly effective in treating type 2 diabetes and obesity. It predominantly stimulates insulin secretion through GLP-1R in mouse islets, but enhances hormone secretion through both incretin receptors in human islets.
Article
Chemistry, Multidisciplinary
Junwei Tang, Wen Peng, Jiangzhou Ji, Chaofan Peng, Tuo Wang, Peng Yang, Ji'ou Gu, Yifei Feng, Kangpeng Jin, Xiaowei Wang, Yueming Sun
Summary: This study reveals that upregulation of GPR176 in colorectal cancer is positively correlated with tumor proliferation and poor overall survival. GPR176 promotes colorectal cancer oncogenesis and development by activating the cAMP/PKA signaling pathway and modulating mitophagy. Mechanistically, GPR176 recruits the GNAS protein intracellularly via its transmembrane helix 3-intracellular loop 2 domain to transduce and amplify extracellular signals from GPR176. The GPR176/GNAS complex inhibits mitophagy via the cAMP/PKA/BNIP3L axis, thereby promoting the tumorigenesis and progression of colorectal cancer.
Review
Pharmacology & Pharmacy
Iona Davies, Tricia M. M. Tan
Summary: With the increasing obesity rates worldwide, there is a critical need for new pharmacotherapies to combat this pandemic. This review focuses on the design of therapeutics targeting the GIPR to facilitate weight loss. The authors highlight the paradoxical finding that both GIPR agonism and antagonism seem to provide metabolic benefits when combined with GLP-1 R agonism, and discuss the therapeutic potential of compounds targeting the GIPR alongside the GLP-1 R and the glucagon receptor.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Mireia Casanovas, Mireia Jimenez-Roses, Arnau Cordomi, Alejandro Lillo, Ignacio Vega-Quiroga, Joan Izquierdo, Mireia Medrano, Katia Gysling, Leonardo Pardo, Gemma Navarro, Rafael Franco
Summary: Cocaine affects dopamine levels in the brain and activates the sigma R-1 receptor, which regulates orexigenic receptor function. The macromolecular complex formed by sigma R-1, D1R, and GHS-R-1a is proposed to be altered by cocaine binding to the sigma R-1, affecting its functionality in coupling to Gs and Gq proteins. The expression of this complex is differentially affected by acute and chronic cocaine administration, potentially allowing dopamine to signal via Ca2+ and ghrelin via cAMP.
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Biochemistry & Molecular Biology
Rafael Franco, Arnau Cordomi, Claudia Llinas del Torrent, Alejandro Lillo, Joan Serrano-Marin, Gemma Navarro, Leonardo Pardo
Summary: This review discusses the occurrence of heteromers formed by different adenosine receptors in mammals, emphasizing the tetrameric structural arrangements and functional diversity they provide to adenosinergic signaling.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Anastassia L. Kantsadi, Emma Cattermole, Minos-Timotheos Matsoukas, Georgios A. Spyroulias, Ioannis Vakonakis
Summary: This article discusses efforts to develop inhibitors for the SARS-CoV-2 main protease and provides detailed information on using STD-NMR spectroscopy to assess the binding of potential M-pro ligands to the viral protease. By making the data public, the goal is to assist in accelerating drug design efforts.
JOURNAL OF BIOMOLECULAR NMR
(2021)
Article
Chemistry, Medicinal
Gemma Navarro, Angel Gonzalez, Adria Sanchez-Morales, Nil Casajuana-Martin, Marc Gomez-Ventura, Arnau Cordomi, Felix Busque, Ramon Alibes, Leonardo Pardo, Rafael Franco
Summary: Cannabidiol (CBD), the second most abundant active compound in the Cannabis sativa plant, is gaining interest for its potential human use as it is neither euphorizing nor addictive. Researchers have designed and synthesized novel compounds based on CBD's properties as a partial agonist and negative allosteric modulator, offering potential therapeutic utility for the cannabinoid CB2 receptor. By using molecular dynamic simulations and site-directed mutagenesis studies, they have identified the allosteric site near the receptor entrance, allowing for structure-guided design of CB2 receptor modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Crystall Swarbrick, Vasiliki Zogali, Kitti Wing Ki Chan, Dimitrios Kiousis, Chin Piaw Gwee, Sai Wang, Julien Lescar, Dahai Luo, Mark von Itzstein, Minos-Timotheos Matsoukas, George Panagiotakopoulos, Subhash G. Vasudevan, Gerasimos Rassias
Summary: The study presents a novel dengue protease inhibitor, SP-471, with high antiviral activity and no cellular toxicity, making it a promising candidate for dengue fever treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Adria Sanchez-Morales, Atilla Bicer, Vasilis Panagiotopoulos, Selma Crecente-Garcia, Cristina Benaiges, Sergi Bayod, Jose Luis Hernandez, Felix Busque, Minos-Timotheos Matsoukas, Merce Perez-Riba, Ramon Alibes
Summary: The Ca2+/calmodulin-mediated phosphatase activity of calcineurin integrates calcium signaling with gene expression programs. In this study, new synthetic compounds were designed and synthesized to inhibit NFATc activity without interfering with CN phosphatase activity. These compounds also showed potential in inhibiting cancer progression.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Iu Raich, Joan Biel Rebassa, Jaume Lillo, Arnau Cordomi, Rafael Rivas-Santisteban, Alejandro Lillo, Irene Reyes-Resina, Rafael Franco, Gemma Navarro
Summary: The study demonstrates the interaction between orexin and CB2R in Alzheimer's disease animal models, forming the CB2-OX1 receptor complex, which may serve as a new therapeutic target for Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Nil Casajuana-Martin, Gemma Navarro, Angel Gonzalez, Claudia Llinas del Torrent, Marc Gomez-Autet, Aleix Quintana Garcia, Rafael Franco, Leonardo Pardo
Summary: Molecular dynamic simulations coupled with site-directed mutagenesis were used to study the binding process of the JWH-133 agonist to the CB2R. A proposed ligand entry pathway was experimentally validated, which is significant for the design of synthetic modulators.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Multidisciplinary Sciences
Adria Sanchez-Morales, Veronique Gigoux, Minos-Timotheos Matsoukas, Laura Perez-Benito, Daniel Fourmy, Ramon Alibes, Felix Busque, Arnau Cordomi, Jean-Marc Devaud
Summary: This article investigates the physiological basis of stress responses in honey bees and designs molecules to alleviate their stress.
SCIENTIFIC REPORTS
(2022)
Article
Virology
Harry Ridgway, Charalampos Ntallis, Christos T. T. Chasapis, Konstantinos Kelaidonis, Minos-Timotheos Matsoukas, Panagiotis Plotas, Vasso Apostolopoulos, Graham Moore, Sotirios Tsiodras, Dimitrios Paraskevis, Thomas Mavromoustakos, John M. M. Matsoukas
Summary: This study reported the variant distribution of SARS-CoV-2 across EU/EEA countries and investigated the driving forces behind mutations that trigger infections. Computational approaches were used to examine the stabilizing effects of key mutations on the RBD-ACE2 complex in Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants. Critical mutations found in the delta variant and two omicron variants were identified, which may contribute to increased transmissibility and morbidity.
Article
Genetics & Heredity
Adrian Garcia-Recio, Jose Carlos Gomez-Tamayo, Iker Reina, Mercedes Campillo, Arnau Cordomi, Mireia Olivella
Summary: The development of TMSNP, a predictor tool dedicated to membrane proteins, combined with a machine-learning model significantly improves the prediction power for determining the pathogenicity of mutations.
NAR GENOMICS AND BIOINFORMATICS
(2021)
Article
Chemistry, Organic
Evangelos Bisyris, Eleni Zingkou, Golfo G. Kordopati, Minos Matsoukas, Plato A. Magriotis, Georgios Pampalakis, Georgia Sotiropoulou
Summary: Kallikrein 7 (KLK7) is a chymotrypsin-like serine protease with established roles in skin diseases, and a new mixed alkyl aryl phosphonate quenched activity-based probe has been developed to potentially monitor its activity.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Evangelos Bisyris, Eleni Zingkou, Golfo G. Kordopati, Minos Matsoukas, Plato A. Magriotis, Georgios Pampalakis, Georgia Sotiropoulou
Summary: A new in silico approach was used to design a kallikrein 7 (KLK7)-specific phosphonate activity-based probe (ABP) for quantifying active KLK7. The epidermal application of the ABP-inhibitor on Netherton syndrome model mice reversed disease hallmarks, showcasing the potential of using ABPs as theranostics.
CHEMICAL COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)