The effect of GLP-1/glucagon 'dual agonists' on amino acid metabolism: potential side effects and solutions

胃泌酸调节素（Oxyntomodulin，OXM）是一种在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血糖水平。这是因为OXM结合了其他两种激素，胰高血糖素样肽-1（GLP-1）和胰高血糖素的作用，导致：1.减少进食量，导致体重减轻。2.改善胰腺释放胰岛素和降低血糖水平。3.增加身体的能量消耗，这有助于减肥。 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患者。这些是GLP-1/胰高血糖素“双重激动剂”。然而，对这些双重激动剂的研究集中在它们对体重和血糖水平的影响上，而忽视了身体的其他同样重要的组成部分，如肌肉，它包含了我们体内的大部分蛋白质。我们知道胰高血糖素导致蛋白质（氨基酸）的构建块的分解。当胰高血糖素过量时，患者会失去大量肌肉并变得更虚弱。我们自己的研究表明，OXM具有类似的作用，因为它具有胰高血糖素样作用，导致氨基酸分解。这可能会导致肌肉蛋白质的损失，以恢复循环氨基酸。如果OXM和“双重激动剂”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，特别是因为我们知道糖尿病患者体内的肌肉相对于脂肪水平已经较低。 因此，该项目旨在研究双重激动剂的作用，提出以下问题：-GLP-1/胰高血糖素双重激动剂是否会导致身体分解氨基酸，导致肌肉损失？- 这种影响与能量消耗的增加有关吗？- 高蛋白饮食可以逆转肌肉损失吗？ 了解这些问题的答案对于在患者中广泛使用这些新的“双重激动剂”之前确定其安全性非常重要，并且还可以使我们通过简单的饮食改变来预防问题。

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.