后膜区 GFRAL 的急性激活有助于葡萄糖调节,与体重无关。

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetes Pub Date : 2023-12-08 DOI:10.2337/db23-0705
Song-Yang Zhang, Zahra Danaei, Kyla Bruce, Jennifer F.M. Chiu, Tony K.T. Lam
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引用次数: 0

摘要

GDF15通过激活在大脑后区表达的受体GFRAL来调节啮齿类动物的能量平衡和葡萄糖稳态。然而,后脑区的 GDF15-GFRAL 信号是否能调节葡萄糖耐量,而不受食物摄入量和体重变化的影响,以及是否有助于二甲双胍的降糖作用,目前仍是未知数。在此,我们报告了在清醒、不受约束和无应激的条件下,将 GDF15 直接急性注入高脂喂养大鼠后膜区可提高静脉葡萄糖耐量和胰岛素敏感性,从而降低肝糖生成,而与食物摄入量、体重和血浆胰岛素水平的变化无关。与此同时,二甲双胍输注可同时提高血浆 GDF15 水平和葡萄糖耐量。最后,敲除后膜区 GFRAL 的表达不仅会抑制 GDF15 的施用,还会抑制二甲双胍增加葡萄糖耐量,而与食物摄入量、体重和血浆胰岛素水平的变化无关。总之,后膜区 GFRAL 的激活有助于体内 GDF15 和二甲双胍的葡萄糖调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acute activation of GFRAL in the area postrema contributes to glucose regulation independent of weight.
GDF15 regulates energy balance and glucose homeostasis in rodents by activating its receptor GFRAL expressed in the area postrema of the brain. However, whether GDF15-GFRAL signaling in the area postrema regulates glucose tolerance independent of changes in food intake and weight and contributes to the glucose-lowering effect of metformin remain unknown. Herein, we report that direct acute GDF15 infusion into the area postrema of high fat fed rats increased intravenous glucose tolerance and insulin sensitivity to lower hepatic glucose production independent of changes in food intake, weight, and plasma insulin levels under conscious, unrestrained, and non-stressed conditions. In parallel, metformin infusion concurrently increased plasma GDF15 levels and glucose tolerance. Finally, a knockdown of GFRAL expression in the area postrema not only negated administration of GDF15 but also metformin to increase glucose tolerance independent of changes in food intake, weight, and plasma insulin levels. In summary, activation of GFRAL in the area postrema contributes to glucose regulation of GDF15 and metformin in vivo.
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
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