Do gut hormones mediate the beneficial effects of Roux-en-Y bypass surgery?

肠道激素是否会介导 Roux-en-Y 搭桥手术的有益效果？

• 批准号: MR/K02115X/1
• 负责人: Stephen Bloom
• 金额: $ 327.22万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK02115X%2F1
• 关键词: Do; gut; hormones; mediate; beneficial

Obesity and diabetes are very common diseases which often go together. Over 1 in 4 people in the UK are obese. Together, these diseases afflict 300 million people and cause an estimated 3 million premature deaths a year. Surgery to reduce weight and especially the "Roux-en-Y gastric bypass" (RYGB) is known to reduce weight and to cure diabetes. Unfortunately surgery can never be the answer to the global problem of obesity and diabetes as it is very expensive, and can cause serious complications. We need a new, cheaper and adjustable treatment for obesity and diabetes that has the benefits of RYGB but without the side effects.Gut hormones are hormones that the bowels make in response to eating. These hormones control our appetite and our metabolism (i.e. the method in which our body uses and stores food). The gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) are much increased in level after RYGB. We believe that this increase in GLP-1, OXM and PYY holds the key to our goal to make a new treatment for obesity and diabetes. If we can prove that by artificially increasing GLP-1, OXM and PYY levels we can help obese diabetic patients to lose weight and to improve their blood sugar levels, this would be a breakthrough in treatment.In this project, we aim to study obese, diabetic patients undergoing the RYGB surgery to see what changes occur in their gut hormone levels, in their metabolism, in their body weight and in their appetite for food. We will compare this to patients who will wear a 'pump' for 28 days. This pump will painlessly deliver a small amount of GLP-1, OXM and PYY via a soft plastic needle under the skin to raise their gut hormone levels. We will see if these pump patients have similar changes to the RYGB group. We will also test out a group of patients to see if similar changes occur when these patients are given a strict low-calorie diet. In this way we hope to understand whether we can make GLP-1, OXM and PYY into a new and better treatment for obesity and diabetes.

肥胖症和糖尿病是非常常见的疾病，经常一起发生。在英国，超过四分之一的人肥胖。这些疾病加在一起影响着3亿人，估计每年造成300万人过早死亡。手术减肥，特别是“Roux-en-Y胃旁路术”（RYGB）是众所周知的减肥和治愈糖尿病。不幸的是，手术永远不能解决肥胖和糖尿病的全球问题，因为它非常昂贵，并可能导致严重的并发症。我们需要一种新的、更便宜的、可调整的肥胖和糖尿病治疗方法，它既有RYGB的好处，又没有副作用。这些激素控制我们的食欲和新陈代谢（即我们的身体使用和储存食物的方法）。RYGB后肠道激素胰高血糖素样肽-1（GLP-1）、胃泌酸调节素（OXM）和肽YY（PYY）的水平显著增加。我们相信，GLP-1、OXM和PYY的增加是我们实现肥胖和糖尿病新治疗目标的关键。如果能够证明通过人工提高GLP-1、OXM和PYY的水平，可以帮助肥胖糖尿病患者减轻体重，改善血糖水平，这将是治疗上的突破。本课题以接受RYGB手术的肥胖糖尿病患者为研究对象，观察他们的肠道激素水平、代谢、体重和食欲发生了什么变化。我们将把这一点与佩戴“泵”28天的患者进行比较。该泵将通过皮肤下的软塑料针头无痛地输送少量GLP-1，OXM和PYY，以提高肠道激素水平。我们将观察这些泵患者是否与RYGB组有相似的变化。我们还将对一组患者进行测试，看看当这些患者接受严格的低热量饮食时是否会发生类似的变化。通过这种方式，我们希望了解我们是否可以使GLP-1，OXM和PYY成为肥胖和糖尿病的新的更好的治疗方法。

项目成果

RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling.

• DOI: 10.1210/en.2016-1755
• 发表时间: 2017-08-01
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Cegla J;Jones BJ;Gardiner JV;Hodson DJ;Marjot T;McGlone ER;Tan TM;Bloom SR
• 通讯作者: Bloom SR

Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: A secondary analysis of a randomized single-blind placebo-controlled study

三肽肠道激素输注不会改变肥胖和糖尿病前期/糖尿病志愿者的食物偏好或甜味功能，但会促进限制饮食：随机单盲安慰剂对照研究的二次分析

• DOI: 10.1111/dom.15028
• 发表时间: 2023
• 期刊: Diabetes, Obesity and Metabolism
• 作者: Behary P

Pharmacokinetics and pharmacodynamics of subcutaneously administered PYY3-36 and its analogues in vivo.

• DOI: 10.1016/s0140-6736(15)60343-9
• 发表时间: 2015-02-26
• 期刊: Lancet (London, England)
• 作者: Cegla, Jaimini;Cuenco, Joyceline;Bloom, Stephen
• 通讯作者: Bloom, Stephen

57-OR: Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Glycaemia and Body Weight in Obesity and Type 2 Diabetes: A Randomized, Single-Blinded Study

57-OR：联合 GLP-1、泌酸调节素和肽 YY 可改善肥胖和 2 型糖尿病患者的血糖和体重：一项随机、单盲研究

• DOI: 10.2337/db19-57-or
• 发表时间: 2019
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: BEHARY P

Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study

• DOI: 10.1136/bmjdrc-2019-001076
• 发表时间: 2020-01-01
• 期刊: BMJ OPEN DIABETES RESEARCH & CARE
• 影响因子: 4.1
• 作者: Alexiadou, Kleopatra;Cuenco, Joyceline;Tan, Tricia M-M
• 通讯作者: Tan, Tricia M-M