Review
Microbiology
Yuan Zeng, Yifan Wu, Qian Zhang, Xinhua Xiao
Summary: The gut microbiota and GLP-1 interact with each other, as gut microbiota metabolites stimulate GLP-1 secretion and affect its function and rhythm. The mechanism of action of GLP-1 on gut microbiota involves inflammatory response. Various interventions can affect the interaction between gut microbiota and GLP-1, which is of great significance for the treatment of metabolic diseases.
Article
Polymer Science
Jingjie Su, Tingting Sun, Yan Wang, Yu Shen
Summary: Molecular dynamics simulation was used to explore the effect of electric field on the structure of Glucagon-like Peptide-2 (GLP-2). The stable α-helix structure of GLP-2 was unwound and transformed into an unstable Turn and Coil structure under the electric field. The degree of unwinding was not linearly related to the electric field intensity, with a maximum at E = 0.5 V/nm. Under weak electric fields, the secondary structure of GLP-2 became looser and chain entropy increased. At a certain electric field strength, the electric force of charged residues reached equilibrium, leading to reduced residue freedom, decreased entropy, increased enthalpy, and enhanced interaction between adjacent residues.
Article
Endocrinology & Metabolism
Khyati Girdhar, Marion Soto, Qian Huang, Lucie Orliaguet, Carly Cederquist, Bharathi Sundaresh, Jiang Hu, Maximilian Figura, Amol Raisingani, Emanuel E. Canfora, Ercument Dirice, Shiho Fujisaka, Gijs H. Goossens, Ellen E. Blaak, Rohit N. Kulkarni, C. Ronald Kahn, Emrah Altindis
Summary: Growing evidence suggests a significant link between gut microbiota, obesity, and metabolic syndrome. The study found that obesity led to changes in pancreatic function, such as increased pancreas weight and altered levels of certain peptides. The alterations in host proteins, particularly pancreatic enzymes, could be reversed by antibiotic treatment. These findings demonstrate that changes in gut microbiota may contribute to the development of obesity and diabetes.
Article
Endocrinology & Metabolism
Yun-Yi Liang, Ling-Yu Liu, Yan Jia, Yi Li, Jie-Na Cai, Yi Shu, Jing-Yi Tan, Pei-Yi Chen, Hong-Wei Li, Hui-Hua Cai, Xiang-Sheng Cai
Summary: This study explored the correlation between gut microbiota and blood biochemical traits, especially GLP-1, in GDM patients. The results showed that there are differences in the gut microbiota between GDM and NGT groups, and certain genera are significantly correlated with blood glucose-related indices. These findings contribute to a better understanding of the pathogenesis of GDM and may provide new insights for its treatment.
WORLD JOURNAL OF DIABETES
(2022)
Article
Chemistry, Medicinal
Neng Jiang, Lin Jing, Qing Li, Sibiao Su, Qimeng Yang, Feng Zhou, Xinyu Chen, Jing Han, Chunli Tang, Weizhong Tang
Summary: Dual activation of the glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) can potentially lead to effective therapy for diabetes and obesity. Novel peptides with dual activity on GLP-1R and GCGR were discovered through rational design, with xGLP/GCG-15 showing promising anti-obesity and anti-diabetic effects in preclinical studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Yingge Li, Xiaoya Zhou, Chen Cheng, Guangming Ding, Peng Zhao, Kai Tan, Lixia Chen, Norbert Perrimon, Jan A. Veenstra, Luoying Zhang, Wei Song
Summary: Severe sleep deprivation is associated with systemic energy wasting, and in this study, it was found that the gut-peptide hormone AstA plays an essential role in mediating this energy wasting. AstA promotes the release of the adipokinetic hormone Akh, which mobilizes systemic energy reserves. This regulation of energy metabolism by AstA was observed in both flies and mice, and the molecular mechanisms involved were also elucidated.
Review
Pharmacology & Pharmacy
Baocheng Xie, Shichun Chen, Yongxiang Xu, Weichao Han, Runkai Hu, Minyi Chen, Yusheng Zhang, Shaobo Ding
Summary: Diabetes mellitus and osteoporosis are closely related, and GLP-1RAs may help in controlling blood sugar levels and promoting bone formation, but more research is needed to clarify their specific effects and mechanisms.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Ying Wang, Haiyi Liu, Miaoyan Zheng, Yanhui Yang, Huizhu Ren, Yan Kong, Shanshan Wang, Jingyu Wang, Yingying Jiang, Juhong Yang, Chunyan Shan
Summary: Berberine may be beneficial in slowing down the progression from prediabetes to type 2 diabetes mellitus in ZDF rats by improving GLP-2 secretion, intestinal permeability, and gut microbiota structure.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Majid Mufaqam Syed-Abdul, Priska Stahel, Alyssa Zembroski, Lili Tian, Changting Xiao, Avital Nahmias, Ian Bookman, Kimberly K. Buhman, Gary F. Lewis
Summary: GLP-2 increases CM secretion without mobilizing CLDs in the intestine. Proteomic analysis identified potential proteins involved in GLP-2-mediated CM secretion. This suggests that GLP-2 enhances CM secretion through a different mechanism than glucose.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Integrative & Complementary Medicine
Li Qiang, Yang Qimeng, Han Jing, Liu Xiaohan, Fu Junjie, Yin Jian
Summary: Peptide dual agonists that target both GLP-1R and GCGR receptors have emerged as potential therapeutics for treating type 2 diabetes with obesity. O-GlcNAcylation was shown to improve the stability of a dual GLP-1R/GCGR agonist, leading to significant weight loss and hypoglycemic effects.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Sport Sciences
Yung-Chih Chen, Jean-Philippe Walhin, Aaron Hengist, Javier T. Gonzalez, James A. Betts, Dylan Thompson
Summary: Interrupting prolonged sitting with intermittent walking can increase postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Microbiology
Dongyue Li, Yanhong Gao, Lanrong Cui, Yang Li, Hao Ling, Xin Tan, Hongyu Xu
Summary: This study investigated the potential targets and protective effects of glucagon-like peptide-2 (GLP-2) in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice through integrative analysis. The results showed that GLP-2 could reduce inflammation by inhibiting potential targets in the NF-kappa B and JAK/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity. This study provides new insight into the potential use of GLP-2 for achieving more ideal UC treatment goals in the future.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Nutrition & Dietetics
Guifang Deng, Qiucheng Lei, Xuejin Gao, Yupeng Zhang, Huazhen Zheng, Jingcheng Bi, Xinying Wang
Summary: The study demonstrates that GLP-2 alleviates gut inflammation and improves enteric Paneth cells immune responses through improving the functioning of epithelial protection and repair, and reducing mucosal inflammatory responses.
FRONTIERS IN NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Tiina Vesterinen, Elina Peltola, Helena Leijon, Paeivi Hannula, Heini Huhtala, Markus J. Makinen, Lasse Nieminen, Elina Pirinen, Mikko Ronty, Mirva Soderstrom, Pia Jaatinen, Johanna Arola
Summary: This study found that the lack of GLP-1R expression in insulinomas is associated with metastatic disease and impaired prognosis. GLP-1R expression could be a useful biomarker in estimating the metastatic potential and prognosis of surgically treated patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria F. Fernandes, Michelle Tomczewski, Robin E. Duncan
Summary: This study found that chronic inflammation leads to reduced GLP-1 secretion and impaired GSIS. Lysophosphatidic acids (LPAs) inhibit GLP-1 secretion in vitro and in vivo through G alpha(i)-coupled LPAR1/3 signaling, linking inflammation with impaired GSIS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Brian P. Cary, Giuseppe Deganutti, Peishen Zhao, Tin T. Truong, Sarah J. Piper, Xinyu Liu, Matthew J. Belousoff, Radostin Danev, Patrick M. Sexton, Denise Wootten, Samuel H. Gellman
Summary: Recent advances in understanding the structures of G-protein-coupled receptors (GPCRs) have highlighted the importance of conformational flexibility in signal propagation. By studying the activation of the GLP-1 receptor, it was found that the conformational plasticity of peptide agonists plays a crucial role in determining agonist efficacy.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tahlia Perry, Alan Stenhouse, Isabella Wilson, Imma Perfetto, Michael W. McKelvey, Michelle Coulson, Rachel A. Ankeny, Peggy D. Rismiller, Frank Grutzner
Summary: The short-beaked echidna, an iconic Australian animal, faces threats such as habitat loss, roads, and invasive species. To gather more information about echidnas Australia-wide, the Echidna Conservation Science Initiative (EchidnaCSI) was established, engaging the public in citizen science research. This project successfully collected a significant amount of echidna data through public participation, demonstrating the potential of citizen science approaches for research on cryptic species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biodiversity Conservation
Alan Stenhouse, Tahlia Perry, Frank Grutzner, Peggy Rismiller, Lian Pin Koh, Megan Lewis
Summary: The COVID-19 pandemic has affected wildlife monitoring, but citizen science observations remain reliable and continuous while traditional scientific monitoring is more affected by the level of restrictions.
BIOLOGICAL CONSERVATION
(2022)
Article
Biochemistry & Molecular Biology
Akihiro Itoigawa, Takashi Hayakawa, Yang Zhou, Adrian D. Manning, Guojie Zhang, Frank Grutzner, Hiroo Imai
Summary: The molecular evolution of bitter taste receptors in egg-laying mammals, such as platypus and echidna, is associated with their feeding habits. The receptive ranges of TAS2Rs differ between the two species, reflecting their distinct diets. Furthermore, the ability to detect beta-glucosides and other substances might be shared and ancestral among mammals.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Pharmacology & Pharmacy
Juliana E. Milburn, Kaleeckal G. Harikumar, Sarah J. Piper, Sweta Raval, Arthur Christopoulos, Denise Wootten, Patrick M. Sexton, Laurence J. Miller
Summary: This study provides a deeper understanding of the activation mechanisms of class B1 G protein-coupled receptors. The interaction between the amino-terminal region of secretin and the seventh transmembrane segment of its receptor plays a structurally specific role, and a charge-charge interaction helps to drive functional activation.
MOLECULAR PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jianjun Cao, Matthew J. Belousoff, Yi-Lynn Liang, Rachel M. Johnson, Tracy M. Josephs, Madeleine M. Fletcher, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton
Summary: The structure and dynamics of AMYRs with amylin and CT were studied, revealing the role of RAMP and the presence of a bypass motif. The binding mechanism of CT-based peptides to AMYRs is distinct from that of amylin-based peptides. This finding has implications for the development of AMYR therapeutics.
Review
Chemistry, Multidisciplinary
Sarah J. Piper, Rachel M. Johnson, Denise Wootten, Patrick M. Sexton
Summary: Membrane proteins are diverse and present different challenges for structure determination. Previous strategies involved engineering or deconstructing the proteins, but recent advances in biochemistry and cryo-electron microscopy allow for high resolution structure determination of various membrane protein groups.
Review
Biochemistry & Molecular Biology
Jessica Lu, Sarah J. Piper, Peishen Zhao, Laurence J. Miller, Denise Wootten, Patrick M. Sexton
Summary: Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides that play important roles in various physiological and pathological processes by activating specific receptors. The structural similarities between these peptides and their receptors present challenges in designing selective therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Tahlia Perry, Ella West, Raphael Eisenhofer, Alan Stenhouse, Isabella Wilson, Belinda Laming, Peggy Rismiller, Michelle Shaw, Frank Gruetzner
Summary: The study investigates and compares the gut microbiomes of captive and wild short-beaked echidnas in Australia. The results show significant differences in microbiome composition between captive and wild populations, highlighting the importance of diet in shaping the gut microbiomes of echidnas.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Endocrinology & Metabolism
Brian P. Cary, Xin Zhang, Jianjun Cao, Rachel M. Johnson, Sarah J. Piper, Elliot J. Gerrard, Denise Wootten, Patrick M. Sexton
Summary: G protein-coupled receptors (GPCRs), particularly the B1 class, play a critical role in maintaining homeostasis and are important drug targets. Recent advances in cryo-electron microscopy have provided valuable insights into the structure and dynamics of these receptors, which contribute to our understanding of their functions.
Article
Multidisciplinary Sciences
Florent Murat, Noe Mbengue, Sofia Boeg Winge, Timo Trefzer, Evgeny Leushkin, Mari Sepp, Margarida Cardoso-Moreira, Julia Schmidt, Celine Schneider, Katharina Moessinger, Thoomke Bruening, Francesco Lamanna, Meritxell Riera Belles, Christian Conrad, Ivanela Kondova, Ronald Bontrop, Ruediger Behr, Philipp Khaitovich, Svante Paeaebo, Tomas Marques-Bonet, Frank Gruetzner, Kristian Almstrup, Mikkel Heide Schierup, Henrik Kaessmann
Summary: Through evolutionary analysis of single-nucleus transcriptome data from 11 species, it was found that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions, and new genes in late spermatogenic stages. The study also revealed that genes predominantly expressed in spermatogonia and Sertoli cells accumulated on X chromosomes during evolution, possibly due to male-beneficial selective forces. Additionally, it was discovered that meiotic sex-chromosome inactivation (MSCI) is an ancestral feature in mammalian sex-chromosome systems, including monotremes.
Correction
Biochemistry & Molecular Biology
Alexander S. Powers, Vi Pham, Wessel A. C. Burger, Geoff Thompson, Yianni Laloudakis, Nicholas W. Barnes, Patrick M. Sexton, Steven M. Paul, Arthur Christopoulos, David M. Thal, Christian C. Felder, Celine Valant, Ron O. Dror
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexander S. Powers, Vi Pham, Wessel A. C. Burger, Geoff Thompson, Yianni Laloudakis, Patrick M. Sexton, Steven M. Paul, Arthur Christopoulos, David M. Thal, Christian C. Felder, Celine Valant, Ron O. Dror
Summary: The selectivity of a drug for target receptors is crucial but challenging when the receptors are similar. Serendipitous discovery of ligands that stimulate target receptors more strongly than closely related receptors provides a solution. This study reveals the structural basis for the efficacy-driven selectivity of xanomeline, a clinical drug candidate, between closely related muscarinic acetylcholine receptors (mAChRs), using atomic-level simulations. The results suggest strategies for rational design of ligands achieving efficacy-driven selectivity for G-protein-coupled receptors.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Cell Biology
Sara Ataie-Ashtiani, Briony Forbes
Summary: The discovery and therapeutic application of insulin hormone over 100 years ago was a significant breakthrough in medicine and medical research. Extensive investigations into the structure and function of insulin, insulin tyrosine kinase receptor (IR), and the signalling cascades upon insulin binding have revealed its multiple roles in cell metabolism and growth. This review discusses insulin gene mutations causing disease and their structural implications, with over 70 mutations identified from more than 100 studies. Understanding these mutations and their pathophysiology is crucial in deciphering the molecular mechanisms of impaired insulin biosynthesis and insulin-IR interaction.
Article
Multidisciplinary Sciences
Wessel A. C. Burger, Vi Pham, Ziva Vuckovic, Alexander S. Powers, Jesse I. Mobbs, Yianni Laloudakis, Alisa Glukhova, Denise Wootten, Andrew B. Tobin, Patrick M. Sexton, Steven M. Paul, Christian C. Felder, Radostin Danev, Ron O. Dror, Arthur Christopoulos, Celine Valant, David M. Thal
Summary: The M4 muscarinic acetylcholine receptor is a significant drug target for the treatment of psychosis, cognition, and addiction. The clinical trial of xanomeline has shown promise in improving symptoms and the cryo-EM structure reveals the binding mechanism, providing insight into its complex pharmacology.
NATURE COMMUNICATIONS
(2023)