The novel GLP-1/GIP dual receptor agonist DA3-CH is neuroprotective in the pilocarpine-induced epileptogenesis rat model

Tian, Miao-Jing; Wang, Ruifang; Hölscher, Christian; Mi, Rulin; Yuan, Zhenyu; Li, Dongfang; Xue, Gui

doi:10.1016/j.eplepsyres.2019.05.008

Cited by 14 publications

(8 citation statements)

References 47 publications

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“…257 Dual incretin receptor agonists. [259][260][261] Evolving understanding of the enteroendocrine cell biology, gut microbiota, and endocannabinoid system [125][126][127] A randomized, placebo-controlled and active comparator-controlled Phase II trial was reported for one of these dual incretin receptor agonists, LY3298176, in patients with type 2 diabetes.…”

Section: Safety Issues and Tolerabilitymentioning

confidence: 99%

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Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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Incretins are hormones secreted from enteroendocrine cells after nutrient intake that stimulate insulin secretion from β cells in a glucose‐dependent manner. Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the only two known incretins. Dysregulation of incretin secretion and actions are noted in diseases such as obesity and diabetes. In this review, we first summarize our traditional understanding of the physiology of GIP and GLP‐1, and our current knowledge of the relationships between GIP and GLP‐1 and obesity and diabetes. Next, we present the results from major randomized controlled trials on the use of GLP‐1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes. We conclude with a glimpse of the future with possible complex interactions between nutrients, gut microbiota, the endocannabinoid system, and enteroendocrine cells.

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Section: Safety Issues and Tolerabilitymentioning

confidence: 99%

“…258 There are at least three other dual incretin receptor agonists in various stages of development: NNC0090-2746 (also known as RG7697), DA-JC1, and DA3-CH. [259][260][261]…”

Section: Safety Issues and Tolerabilitymentioning

confidence: 99%

Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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“…Then, 15 μL of the mixed sample was separated by polyacrylamide gel electrophoresis using a Trisine-SDS-PAGE Kit. The western blot step was performed as described 60 ; details on the western blot procedure can be found in the Supplementary Information .…”

Section: Methodsmentioning

confidence: 99%

Two antimicrobial genes from Aegilops tauschii Cosson identified by the Bacillus subtilis expression system

Islam

Ali

et al. 2020

Sci Rep

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Antimicrobial genes play an important role as a primary defense mechanism in all multicellular organisms. We chose Bacillus subtilis as a target pathogen indicator and transferred the Aegilops tauschii Cosson cDNA library into B. subtilis cells. Expression of the candidate antimicrobial gene can inhibit B. subtilis cell growth. Using this strategy, we screened six genes that have an internal effect on the indicator bacteria. Then, the secreted proteins were extracted and tested; two genes, AtR100 and AtR472, were found to have strong external antimicrobial activities with broad-spectrum resistance against Xanthomonas oryzae pv. oryzicola, Clavibacter fangii, and Botrytis cinerea. Additionally, thermal stability tests indicated that the antimicrobial activities of both proteins were thermostable. Furthermore, these two proteins exhibited no significant hemolytic activities. To test the feasibility of application at the industrial level, liquid fermentation and spray drying of these two proteins were conducted. Powder dilutions were shown to have significant inhibitory effects on B. cinerea. Fluorescence microscopy and flow cytometry results showed that the purified protein impaired and targeted the cell membranes. This study revealed that these two antimicrobial peptides could potentially be used for replacing antibiotics, which would provide the chance to reduce the emergence of drug resistance. Antibiotics have been widely used worldwide in recent decades to control many pathogens. Due to the excessive use of antibiotics, many bacteria have already developed antibiotic resistance mechanisms 1,2. Meanwhile, pathogen resistance has become a serious global threat, especially in intensive care units, where resistance often occurs 3,4. The increasing number of multi-drug-resistant pathogens has led to a growing demand for new antibiotics; however, even if new antibiotics are identified, resistance cannot be avoided because of antibiotic overuse, which is the primary cause of antibiotic resistance 5,6. With the increasing use of antibiotics, there is an urgent need to produce something with a negative impact against resistance mechanisms; thus, new therapeutic agents to replace antibiotics must be found. Antimicrobial peptides (AMPs) are potential substitutes for antibiotics because of their broad-spectrum resistance and rare resistant variants 7. These peptides have broad activity against a variety of bacteria, fungi, viruses, parasites, and cancer cells; furthermore, almost all organisms have a variety of broad-spectrum antimicrobial peptides 8. An antimicrobial peptide is an amphiphilic, cationic, and small protein in organisms as well as an important component of the innate immune system 9. The natural immunity of many organisms relies on the invasive power of antimicrobial peptides against different microbes 10. Since some antimicrobial peptides are biologically safe and are not susceptible to drug resistance, more and more of these have been discovered and excavated 11-14 , and the discovery and application of a...

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“…It has been proven that the native peptide GLP-1, GLP-1 receptor agonists and GIP-1 receptor agonists can cross the blood-brain barrier (BBB) ( 57 – 61 ). There is also a rising interest in dual GLP-1R/GIPR agonists as neuroprotective drugs that act on respective homoreceptors located in the central nervous system (CNS), with proof that these peptides could also pass through the BBB ( 62 – 64 ).…”

Section: Glucagon-like Peptide-1 and Glucagon-like Peptide-1 Receptorsmentioning

confidence: 99%

Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research

Yang

Qiang

et al. 2022

Front. Neurol.

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The public and social health burdens of ischemic stroke have been increasing worldwide. Hyperglycemia leads to a greater risk of stroke. This increased risk is commonly seen among patients with diabetes and is in connection with worsened clinical conditions and higher mortality in patients with acute ischemic stroke (AIS). Therapy for stroke focuses mainly on restoring cerebral blood flow (CBF) and ameliorating neurological impairment caused by stroke. Although choices of stroke treatment remain limited, much advance have been achieved in assisting patients in recovering from ischemic stroke, along with progress of recanalization therapy through pharmacological and mechanical thrombolysis. However, it is still necessary to develop neuroprotective therapies for AIS to protect the brain against injury before and during reperfusion, prolong the time window for intervention, and consequently improve neurological prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are broadly regarded as effective drugs in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data on GLP-1 and GLP-1 RAs have displayed an impressive neuroprotective efficacy in stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. Based on the preclinical studies in the past decade, we review recent progress in the biological roles of GLP-1 and GLP-1 RAs in ischemic stroke. Emphasis will be placed on their neuroprotective effects in experimental models of cerebral ischemia stroke at cellular and molecular levels.

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The novel GLP-1/GIP dual receptor agonist DA3-CH is neuroprotective in the pilocarpine-induced epileptogenesis rat model

Cited by 14 publications

References 47 publications

Incretins in obesity and diabetes

Incretins in obesity and diabetes

Two antimicrobial genes from Aegilops tauschii Cosson identified by the Bacillus subtilis expression system

Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research

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