Clinical investigation of glucokinase activators for the restoration of glucose homeostasis in diabetes

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Ping Li, Dalong Zhu
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Abstract

As a sensor, glucokinase (GK) controls glucose homeostasis, which progressively declines in patients with diabetes. GK maintains the equilibrium of glucose levels and regulates the homeostatic system set points. Endocrine and hepatic cells can both respond to glucose cooperatively when GK is activated. GK has been under study as a therapeutic target for decades due to the possibility that cellular GK expression and function can be recovered, hence restoring glucose homeostasis in patients with type 2 diabetes. Five therapeutic compounds targeting GK are being investigated globally at the moment. They all have distinctive molecular structures and have been clinically shown to have strong antihyperglycemia effects. The mechanics, classification, and clinical development of GK activators are illustrated in this review. With the recent approval and marketing of the first GK activator (GKA), dorzagliatin, GKA's critical role in treating glucose homeostasis disorder and its long-term benefits in diabetes will eventually become clear.

Abstract Image

葡萄糖激酶激活剂用于恢复糖尿病患者葡萄糖稳态的临床研究
作为一种传感器,葡萄糖激酶(GK)控制着糖尿病患者体内逐渐下降的葡萄糖平衡。GK 可维持葡萄糖水平的平衡,并调节体内平衡系统的设定点。当 GK 被激活时,内分泌细胞和肝细胞都能对葡萄糖做出协同反应。由于细胞 GK 的表达和功能有可能恢复,从而恢复 2 型糖尿病患者的葡萄糖稳态,几十年来,GK 一直被作为治疗靶点进行研究。目前,全球正在研究五种针对 GK 的治疗化合物。它们都具有独特的分子结构,临床显示具有很强的抗高血糖作用。本综述阐述了 GK 激活剂的机制、分类和临床开发。随着首个 GK 激活剂(GKA)多扎格列汀(dorzagliatin)最近获得批准并上市,GKA 在治疗糖稳态紊乱中的关键作用及其对糖尿病的长期益处终将变得清晰可见。
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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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