Review
Immunology
Syed Faizan Mehdi, Suma Pusapati, Muhammad Saad Anwar, Durga Lohana, Parkash Kumar, Savitri Aninditha Nandula, Fatima Kausar Nawaz, Kevin Tracey, Huan Yang, Derek LeRoith, Michael J. Brownstein, Jesse Roth
Summary: Inflammation is involved in many chronic conditions and stimulates the release of pro-inflammatory cytokines and immune cells. GLP-1 levels are associated with disease severity and can serve as markers of inflammation. Previous studies have investigated the anti-inflammatory properties of oxytocin, hCG, ghrelin, alpha-MSH and ACTH, while the anti-inflammatory effects of GLP-1 have only recently been recognized. GLP-1 has been shown to be beneficial in treating type-2 diabetes, metabolic syndrome, and hyperglycemia by reducing inflammation and cell death.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Endocrinology & Metabolism
Christophe E. M. De Block, Eveline Dirinck, Ann Verhaegen, Luc F. Van Gaal
Summary: Glucagon-like peptide-1 receptor agonists and dual GLP-1/glucose-dependent insulinotropic peptide RA tirzepatide have expanded the population of individuals reaching HbA1c and weight targets, showing potential therapeutic benefits. However, further research is needed to determine whether this will lead to improved cardiovascular outcomes and impact treatment guidelines.
DIABETES OBESITY & METABOLISM
(2022)
Review
Endocrinology & Metabolism
Carmen M. Labandeira, Arturo Fraga-Bau, David Arias Ron, Ana Munoz, Gema Alonso-Losada, Antonio Koukoulis, Jesus Romero-Lopez, Ana Rodriguez-Perez
Summary: Parkinson's disease and diabetes mellitus are two chronic disorders associated with aging that are increasingly prevalent worldwide. Research has shown that insulin plays a role in the brain that may affect the development of Parkinson's disease, and some antidiabetic treatments may have a certain impact on this disease.
FRONTIERS IN NEUROENDOCRINOLOGY
(2021)
Article
Medicine, Research & Experimental
Cristina Bouzas, Rosario Pastor, Silvia Garcia, Margalida Monserrat-Mesquida, Miguel Angel Martinez-Gonzalez., Jordi Salas-Salvado, Dolores Corella, Albert Goday, J. Alfredo Martinez, Angel M. Alonso-Gomez, Olga Fernandez-Barcelo, Jesus Vioque, Dora Romaguera, Jose Lopez-Miranda, Ramon Estruch, Francisco J. Tinahones, Jose Lapetra, Lluis Serra-Majema, Blanca Riquelme-Gallegop, Vicente Martin-Sanchez, Xavier Pinto, Miguel Delgado-Rodriguez, Pilar Matia, Josep Vidal, Jersy-Jair Cardenas-Salas, Lidia Daimiel, Emilio Ros, Estefania Toledo, Josep M. Manzanares, Inmaculada Gonzalez-Monge, Miguel-Angel Munoz, Diego Martinez-Urbistondo, Lucas Tojal-Sierra, Carlos Munoz-Bravoaf, Salvador Miralles-Gisbert, Marian Martin, Antonio Garcia-Rios, Sara Castro-Barquero, Jose Carlos Fernandez-Garcia, Jose Manuel Santos-Lozano, F. Javier Basterra-Gortari, Liliana Gutierrez-Carrasquilla, Patricia Guillem-Saiz, Alba Satorres, Itziar Abete, Carolina Sorto-Sanchez, Javier Diez-Espino, Nancy Babio, Montse Fito, Josep A. Tur
Summary: In a one-year study involving 6881 patients with MetS, it was found that those treated with GLP-1RA and DPP-4I had better glycemic profiles, but improvements in weight and waist circumference were modest.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Jun Chen, Aihua Mei, Xinxin Liu, Zachary Braunstein, Yingying Wei, Biao Wang, Lihua Duan, Xiaoquan Rao, Sanjay Rajagopalan, Lingli Dong, Jixin Zhong
Summary: This study confirms the expression of GLP-1R in macrophages in inflammatory diseases. Deficiency of GLP-1R reduces macrophage migration and enhances interleukin-6 expression. In a gout model, recruitment of macrophages is suppressed in GLP-1R knockout mice.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zara J. Franklin, Ryan A. Lafferty, Peter R. Flatt, Laura M. McShane, Finbarr P. M. O'Harte, Nigel Irwin
Summary: Ablation of GCGR signaling and activation of the GLP-1 receptor significantly improve metabolism in HFF mice, but combination therapy does not show obvious additional benefits.
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
Behavioral Sciences
Ningxiang Zeng, Elam J. Cutts, Christian B. Lopez, Simran Kaur, Miguel Duran, Sonja A. Virkus, J. Andrew Hardaway
Summary: The study deeply characterized the pattern of Glp1r in the CeA and studied the neurophysiological characteristics of CeA neurons expressing Glp1r. Glp1r(CeA) cells are highly enriched in the medial subdivision of the CeA (CeM) and exhibit unique characteristics in terms of neuronal activity. These findings will be crucial for further understanding the impact of GLP-1R agonists on feeding and motivation.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Review
Cardiac & Cardiovascular Systems
Bruno Verges, Victor Aboyans, Denis Angoulvant, Pierre Boutouyrie, Bertrand Cariou, Fabien Hyafil, Kamel Mohammedi, Pierre Amarenco
Summary: This review summarizes the potential mechanisms by which glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide stroke protection in patients with diabetes. GLP-1RAs show multiple anti-atherosclerotic effects and reduce traditional stroke risk factors. Additionally, GLP-1RAs demonstrate direct cerebral effects in animal stroke models, promoting neurogenesis and reducing infarct volume.
CARDIOVASCULAR DIABETOLOGY
(2022)
Article
Endocrinology & Metabolism
Fiona M. Gribble, Frank Reimann
Summary: GLP-1, a peptide hormone from the intestinal tract, plays a central role in regulating postprandial glucose homeostasis through insulin secretion, food intake, and gut motility. It serves as the basis for a variety of current drugs for treating type 2 diabetes and obesity, and is also the focus of new drug development.
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)
Review
Pharmacology & Pharmacy
Johanna Helmstaedter, Karin Keppeler, Leonie Kuester, Thomas Muenzel, Andreas Daiber, Sebastian Steven
Summary: Cardiovascular outcome trials have shown cardiovascular benefits for type 2 diabetes mellitus patients treated with long-acting GLP-1 receptor agonists. However, the effects of GLP-1 and receptor agonists on the cardiovascular system are not fully understood. Further research is needed to explore the potential cardiovascular protection beyond glycaemic control offered by GLP-1 receptor agonists.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Chloe Wong, Ming Hui Lee, Clyve Yu Leon Yaow, Yip Han Chin, Xin Lei Goh, Cheng Han Ng, Amanda Yuan Ling Lim, Mark Dhinesh Muthiah, Chin Meng Khoo
Summary: This meta-analysis examined the efficacy of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Results showed significant improvements in hepatic fat content, liver biochemistry, body composition, glucose parameters, lipid parameters, insulin sensitivity, and inflammatory markers following treatment with glucagon-like peptide-1 receptor agonists. Glucagon-like peptide-1 receptor agonists were also found to significantly decrease hepatic fat content compared to other treatments, showing promise in improving both diabetes and non-alcoholic fatty liver disease phenotype.
FRONTIERS IN ENDOCRINOLOGY
(2021)
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
Pharmacology & Pharmacy
Katherine O. Kopp, Elliot J. Glotfelty, Yazhou Li, Nigel H. Greig
Summary: Chronic neuroinflammation is a key feature of neurodegenerative diseases, and targeting this inflammation has not been effectively utilized in clinical treatments. The risk of inflammation and neurodegenerative diseases is associated with type 2 diabetes and insulin resistance, suggesting that alleviating diabetes pathology may help treat neuroinflammation and neurodegeneration. GLP-1 is a hormone that promotes healthy insulin signaling and has shown anti-inflammatory, neurotrophic, and neuroprotective properties in preclinical neurodegenerative disease models.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: GLP-1, as an important incretin hormone, has made significant progress in drug development and clinical application, offering a wide range of metabolic benefits. With the clinical approval and continuous evolution of GLP-1 receptor ligands, it is expected that GLP-1 has great potential in treating diseases beyond diabetes and obesity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
D. Sarnobat, R. C. Moffett, P. R. Flatt, A. I. Tarasov
Summary: The study showed that metformin and rosiglitazone can help slow down the reduction of beta-cell pool in streptozotocin-induced diabetes, while tolbutamide may exacerbate beta-cell apoptosis but potentially protect beta-cells from chronic hyperglycemia by increasing insulin secretion directly.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2022)
Article
Endocrinology & Metabolism
Neil Tanday, Ryan A. Lafferty, Peter R. Flatt, Nigel Irwin
Summary: Sequential administration of SL-PYY and liraglutide showed improvements in energy intake, body weight, glucose and insulin levels in diabetic mice. Additionally, the combination therapy enhanced insulin sensitivity and modulated pancreatic hormones, suggesting potential as a treatment option for diabetes.
DIABETES OBESITY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ryan A. Lafferty, Laura M. McShane, Zara J. Franklin, Peter R. Flatt, Finbarr P. M. O'Harte, Nigel Irwin
Summary: In this study, the metabolic benefits of two glucagon receptor antagonists were evaluated in insulin-resistant high-fat-fed mice. The results showed that these antagonists can decrease blood glucose levels, reduce food intake, and improve glucose tolerance. These data provide further evidence that peptidic GCGR antagonists are effective treatment options for obesity-driven forms of diabetes.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wuyun Zhu, Neil Tanday, Peter R. Flatt, Nigel Irwin
Summary: Pancreatic polypeptide (PP), a member of the neuropeptide Y (NPY) family, acts as a hormone secreted by the endocrine pancreas to regulate appetite. It induces satiety through activation of hypothalamic NPY4 receptors, suggesting potential anti-obesity effects. PP also has effects on the endocrine pancreas, including insulinostatic and possibly anti-diabetic actions through Y1 and Y4 receptors. However, the short half-life of PP limits its therapeutic potential as an anti-obesity and anti-diabetes drug target, requiring the development of long-acting forms of PP.
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, SWM. Dobbin, N. Tanday, VA. Gault, S. McClean, N. Irwin
Summary: Research has shown that a novel peptide, Delta-TRTX-AC1, isolated from the venom of the Mexican Blond tarantula spider, has potential therapeutic benefits for diabetes. It has been found to promote insulin secretion, enhance beta-cell proliferation, and protect against apoptosis. In animal experiments, Delta-TRTX-AC1 was shown to decrease blood glucose levels and suppress appetite. Additionally, it augmented the appetite-suppressing effects of exenatide.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Julie Turbitt, Lorraine Brennan, R. Charlotte Moffett, Peter R. Flatt, Paul R. V. Johnson, Andrei I. Tarasov, Neville H. McClenaghan
Summary: The study found that taurine, alanine, and proline can promote insulin secretion through the regulation of ion transport and inhibition of the sodium-potassium-chloride cotransporter. This action of taurine may have potential value in the treatment of diabetes.
Article
Cell Biology
Ryan Lafferty, Neil Tanday, Vaibhav Dubey, Aimee Coulter-Parkhill, Karthick Vishal, Charlotte Moffett, Finbarr O'Harte, Peter R. Flatt, Nigel Irwin
Summary: This study investigates the effects of glucagon receptor antagonists on alpha-cell turnover and lineage in mice, and finds that the effects are dose-related. The results show that low-dose glucagon receptor antagonists can help restore the changes in alpha-cell mantle in mice, while high-dose treatment promotes alpha-cell to beta-cell transdifferentiation.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Ananyaa Sridhar, Dawood Khan, Jessie A. Elliott, Violetta Naughton, Peter R. Flatt, Nigel Irwin, Charlotte R. Moffett
Summary: This pilot study investigated the effects of Roux-en-Y gastric bypass (RYGB) surgery on intestinal morphology and gut-cell hormone expression profile in rats fed high-fat-diet (HFD) and normal-diet (ND). The results showed that the bypassed biliopancreatic-limb (BPL) maintained normal morphology and unchanged enteroendocrine cell populations, while the alimentary-limbs (AL) had enhanced villi area and increased numbers of GLP-2 positive cells in ND rats and decreased expression of PYY in HFD rats.
Review
Endocrinology & Metabolism
Neil Tanday, Andrei I. Tarasov, R. Charlotte Moffett, Peter R. Flatt, Nigel Irwin
Summary: The development of pancreatic islet endocrine cells is tightly regulated, and small changes in the environment can lead to the generation of different cell types with distinct hormones. Cell differentiation is driven by transcription factors, which are also critical for maintaining mature islet cell phenotype. Prolonged metabolic stress can alter the transcription factor set of insulin-secreting beta cells, leading to loss of beta-cell identity through de- or transdifferentiation. Approved and experimental antidiabetic agents have been associated with preventing beta-cell dedifferentiation or promoting the transdifferentiation of non-beta cells towards an insulin-positive beta-cell-like phenotype. Understanding islet cell plasticity is important for preventing beta-cell decline in diabetes.
DIABETES OBESITY & METABOLISM
(2023)
Article
Pharmacology & Pharmacy
A. Coulter-Parkhill, V. A. Gault, S. McClean, N. Irwin
Summary: This study examined the glucose-lowering potential and mechanisms of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides derived from the venom of the Chinese earth tarantula. The synthetic peptides were non-toxic and increased insulin secretion, beta-cell proliferation, and protected against apoptosis. Although they had no significant effect on blood glucose levels, they enhanced the appetite-suppressive effects of exenatide. These findings highlight the therapeutic potential of venom-derived peptides for the treatment of diabetes and obesity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Neil Tanday, Aimee Coulter-Parkhill, R. Charlotte Moffett, Karthick Suruli, Vaibhav Dubey, Peter R. Flatt, Nigel Irwin
Summary: The study compares the metabolic and pancreatic islet adaptative responses between male and female mice after the administration of STZ and HC. The results show that both STZ and HC induce hyperglycemia and insulin resistance, but there are differences in pancreatic islet morphology and cell apoptosis between males and females.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ananyaa Sridhar, Dawood Khan, Peter R. Flatt, Charlotte R. Moffett, Nigel Irwin
Summary: This study aims to evaluate the effects of 21-day twice daily treatment with a glucagon-like peptide-1 receptor agonist and a glucose-dependent insulinotropic peptide receptor antagonist on intestinal morphology and related gut hormones in obese mice. The results show that these treatment interventions can improve intestinal morphology and restore levels of gut hormones in high fat diet mice, which may be linked to metabolic benefits.