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
Oncology
Noriko Tagawa, Honoka Ogura, Hikaru Miyawaki, Akihiro Asakawa, Ikuo Kato
Summary: This study found that peripheral administration of nesfatin-1 increased blood concentrations of GLP-1 and insulin, and decreased blood glucose concentrations in food-deprived mice. Furthermore, the study demonstrated that nesfatin-1 increased insulin concentrations by accelerating GLP-1 secretion. These findings suggest the potential therapeutic value of nesfatin-1 for GLP-1 release.
MOLECULAR MEDICINE REPORTS
(2023)
Article
Pharmacology & Pharmacy
Anubhav Pratap-Singh, Yigong Guo, Alberto Baldelli, Anika Singh
Summary: Injectable peptides like insulin and GLP-1 are commonly used for diabetes treatment, but injection administration has disadvantages. Buccal and sublingual routes are valid alternatives due to their accessibility, but there are challenges in peptide selection, drug encapsulation, and delivery system design. Using hydrophobic polymers and neutral or positively charged nanoparticles can improve drug efficiency and efficacy in buccal delivery. Unidirectional films and tablets show higher bioavailability compared to sprays, mitigating the impact of saliva and enzymatic digestion.
Review
Clinical Neurology
Hussein N. Yassine, Victoria Solomon, Angad Thakral, Nasim Sheikh-Bahaei, Helena C. Chui, Meredith N. Braskie, Lon. S. Schneider, Konrad Talbot
Summary: Medications for type 2 diabetes show potential for interventions in dementia syndromes by addressing the common energy failure in neurons. GLP-1 receptor agonists have protective effects on vascular, microglial, and neuronal functions, making them promising for dementia treatments. The development of these medications as dementia therapies requires a deeper understanding of regional changes in brain energy metabolism guided by novel imaging biomarkers.
ALZHEIMERS & DEMENTIA
(2022)
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)
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.
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
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
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
Chemistry, Medicinal
Yongliang Yuan, Zhiming Yan, Qifang Lao, Neng Jiang, Shuangmin Wu, Qinpei Lu, Jing Han, Songfeng Zhao
Summary: The development of a unimolecular triple agonist peptide targeting GLP-1, glucagon, and Y2 receptors shows great potential as a novel anti-obesity and anti-diabetic agent. This peptide, 3b, demonstrated potent activity in reducing food intake without causing nausea and had better effects on lipid metabolism, body weight, and glycemic control compared to other agonist counterparts. Targeting GLP-1R, GCGR, and Y2R with a unimolecular triple agonist peptide offers a promising route for developing new treatments for obesity and T2DM.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Hematology
Avital Nahmias, Priska Stahel, Lili Tian, Changting Xiao, Gary F. Lewis
Summary: The study found that GLP-1R antagonism enhances intestinal TG output in rats by stimulating lymph flow and increasing lymph TG concentration. This indicates that endogenously secreted GLP-1 after a lipid bolus is sufficient to modulate CM secretion in rats.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Yumie Takeshita, Yuki Kita, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Chisato Teramura, Yasufumi Enyama, Toshinari Takamura
Summary: The study found that GLP-1 receptor agonists can effectively lower blood glucose levels in diabetic patients, even without prior glycemic control. However, for insulinopenic type 2 diabetes patients, prior glycemic control with insulin may help overcome glucose toxicity-induced GLP-1 resistance.
JOURNAL OF DIABETES INVESTIGATION
(2022)
Article
Endocrinology & Metabolism
Wanjun Guo, Zheng Xu, Haixia Zou, Feng Li, Yao Li, Jing Feng, Zhiyi Zhu, Qing Zheng, Rui Zhu, Bin Wang, Yan Li, Sujuan Hao, Hong Qin, Catherine L. Jones, Eric Adegbite, Libnir Telusca, Martijn Fenaux, Weidong Zhong, Mohammed K. Junaidi, Susan Xu, Hai Pan
Summary: This study discovered and characterized a novel GLP-1 analog called Ecnoglutide. Through experiments and clinical trials, it was found that Ecnoglutide showed better effects in reducing blood glucose, inducing insulin, and promoting weight loss compared to semaglutide, and it demonstrated good safety and tolerability.
MOLECULAR METABOLISM
(2023)