The effect of GLP-1/glucagon 'dual agonists' on amino acid metabolism: potential side effects and solutions
GLP-1/胰高血糖素“双重激动剂”对氨基酸代谢的影响:潜在副作用和解决方案
基本信息
- 批准号:MR/S02171X/1
- 负责人:
- 金额:$ 39.89万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2019
- 资助国家:英国
- 起止时间:2019 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Oxyntomodulin (OXM) is a natural hormone released from the gut following eating. We know that OXM can reduce weight and improve blood sugar levels in people with diabetes. This is because OXM combines the effects of two other hormones, glucagon-like peptide-1 (GLP-1) and glucagon, leading to: 1. A reduction in the amount of food eaten, leading to weight loss. 2. Improved release of insulin by the pancreas and lower sugar levels. 3. Increased energy expenditure by the body which helps with weight loss. Drug companies are currently developing medications based on OXM to help patients with diabetes and obesity. These are the GLP-1/glucagon 'dual agonists'. However, the research on these dual agonists has concentrated on their effects on body weight and blood glucose levels and has neglected other equally important components of the body such as the muscles, which contain most of the protein in our bodies. We know that glucagon leads to a breakdown of the building blocks of proteins (amino acids). Where glucagon occurs in excess, patients lose a great deal of muscle and become weaker. Our own research shows that OXM has a similar effect because of its glucagon-like effects, leading to breakdown of amino acids. This may cause loss of muscle protein to restore circulating amino acids. If OXM and 'dual agonists' lead to breakdown of amino acids and muscle loss this could cause serious health problems, particularly as we know that diabetic patients already have a lower level of muscle relative to fat in their bodies. Therefore, this project aims to investigate the effect of dual agonists, asking the following questions: - Does the GLP-1/glucagon dual agonist cause the body to break down amino acids, resulting in loss of muscle? - Is this effect associated with the increase in energy expenditure? - Can the muscle loss be reversed by a high-protein diet? Knowing the answer to these questions is important to establishing the safety of these new 'dual agonists' prior to their widespread use in patients and may also allow us to prevent problems with a simple dietary change.
氧合酶调节蛋白(OXM)是一种进食后从肠道释放的天然激素。我们知道OXM可以减轻糖尿病患者的体重并改善其血糖水平。这是因为OXM结合了另外两种激素--胰高血糖素样肽-1(GLP-1)和胰高血糖素,导致:1.减少进食量,导致体重减轻。2.改善胰腺对胰岛素的释放,降低血糖水平。3.身体能量消耗增加,有助于减肥。制药公司目前正在开发基于OXM的药物,以帮助糖尿病和肥胖症患者。这些是GLP-1/胰高血糖素‘双激动剂’。然而,对这些双重激动剂的研究主要集中在它们对体重和血糖水平的影响上,而忽略了身体的其他同样重要的组成部分,如肌肉,它们包含了我们身体中的大部分蛋白质。我们知道,胰高血糖素会导致蛋白质(氨基酸)组成成分的分解。如果胰高血糖素过多,患者就会失去大量肌肉,变得虚弱。我们自己的研究表明,OXM具有类似的作用,因为它具有类胰高血糖素的作用,导致氨基酸分解。这可能会导致肌肉蛋白质的损失,以恢复循环中的氨基酸。如果OXM和‘双激动剂’导致氨基酸分解和肌肉损失,这可能会导致严重的健康问题,特别是我们知道糖尿病患者体内肌肉相对于脂肪的水平已经较低。因此,本项目旨在研究双激动剂的作用,提出以下问题:-GLP-1/高血糖素双激动剂是否会导致身体分解氨基酸,导致肌肉损失?-这种影响是否与能量消耗的增加有关?-高蛋白饮食能否逆转肌肉损失?了解这些问题的答案对于在患者广泛使用这些新的“双激动剂”之前确定它们的安全性很重要,也可能使我们能够防止简单的饮食改变带来的问题。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215 , in adults with overweight or obesity: Results from a phase 1 randomized clinical trial
胰高血糖素样肽 1/胰高血糖素受体共激动剂 G3215 的适应性输注,用于超重或肥胖的成人:1 期随机临床试验的结果
- DOI:10.1111/dom.15448
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Hope D
- 通讯作者:Hope D
Glucagon and energy expenditure; Revisiting amino acid metabolism and implications for weight loss therapy
- DOI:10.1016/j.peptides.2023.170962
- 发表时间:2023-01
- 期刊:
- 影响因子:3
- 作者:D. Hope;Tuyet M Tan
- 通讯作者:D. Hope;Tuyet M Tan
Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss.
- DOI:10.1016/j.xcrm.2022.100810
- 发表时间:2022-11-15
- 期刊:
- 影响因子:14.3
- 作者:Hope, David C. D.;Hinds, Charlotte E.;Lopes, Tatiana;Vincent, Matthew L.;V. Shrewsbury, Jed;Yu, Arthur T. C.;Davies, Iona;Scott, Rebecca;Jones, Ben;Murphy, Kevin G.;Minnion, James S.;Sardini, Alessandro;Carling, David;Lutz, Thomas A.;Bloom, Stephen R.;Tan, Tricia M. M.;Owen, Bryn M.
- 通讯作者:Owen, Bryn M.
Striking the Balance: GLP-1/Glucagon Co-Agonism as a Treatment Strategy for Obesity.
- DOI:10.3389/fendo.2021.735019
- 发表时间:2021
- 期刊:
- 影响因子:5.2
- 作者:Hope DCD;Vincent ML;Tan TMM
- 通讯作者:Tan TMM
A glucagon analogue decreases body weight in mice via signalling in the liver.
- DOI:10.1038/s41598-021-01912-0
- 发表时间:2021-11-19
- 期刊:
- 影响因子:4.6
- 作者:Hinds CE;Owen BM;Hope DCD;Pickford P;Jones B;Tan TM;Minnion JS;Bloom SR
- 通讯作者:Bloom SR
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David Hope其他文献
Mucosal boosting increases protective efficacy of an influenza vaccine in mice
黏膜加强免疫可提高流感疫苗在小鼠中的保护效力
- DOI:
10.1016/j.isci.2025.112721 - 发表时间:
2025-06-20 - 期刊:
- 影响因子:4.100
- 作者:
Liping Wang;Chi Ngai Chan;Jayeshbhai Chaudhari;David Hope;Alejandro A. Espinosa Perez;Ninaad Lasrado;Zhenyu Li;Alejandra Waller-Pulido;Dalia N. Cabrera-Barragan;Brookelynne Verette;Samuel J. Nangle;Jose Ayala-Bernot;Catherine Jacob-Dolan;Michelle Lifton;Ellis Strutton;Jana Fisher;Esther Mbiwan;Annika Rossler;Sara Schrag;Dan H. Barouch - 通讯作者:
Dan H. Barouch
Is There a Replication Crisis in Medical Education Research?
医学教育研究是否存在复制危机?
- DOI:
10.1097/acm.0000000000004063 - 发表时间:
2021 - 期刊:
- 影响因子:7.4
- 作者:
David Hope;Avril Dewar;Christopher Hay - 通讯作者:
Christopher Hay
Household education gaps and gender role attitudes
家庭教育差距和性别角色态度
- DOI:
10.1017/psrm.2021.16 - 发表时间:
2021 - 期刊:
- 影响因子:3.9
- 作者:
Marco Giani;David Hope;Ø. Skorge - 通讯作者:
Ø. Skorge
Minor Physical Anomalies, Intelligence, and Cognitive Decline
轻微的身体异常、智力和认知能力下降
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:1.8
- 作者:
David Hope;Timothy C. Bates;A. Gow;J. Starr;I. Deary - 通讯作者:
I. Deary
Medical students’ understanding of cost effectiveness in feedback delivery
医学生对反馈传递成本效益的理解
- DOI:
10.15694/mep.2019.000026.1 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
F. Mahmood;David Hope;H. Cameron - 通讯作者:
H. Cameron
David Hope的其他文献
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