Zhengli Bai, Ke Wang, Tiffany Yau, Cadmon K P Lim, Sandra T F Tsoi, Baoqi Fan, Claudia H T Tam, Emily W M Poon, Andrea O Y Luk, Alice P S Kong, Ronald C W Ma, Ele Ferrannini, Andrea Mari, Li Chen, Juliana C N Chan, Elaine Chow
{"title":"葡萄糖激酶激活剂Dorzagliatin对糖耐量受损和正常个体α-和β-细胞功能的影响","authors":"Zhengli Bai, Ke Wang, Tiffany Yau, Cadmon K P Lim, Sandra T F Tsoi, Baoqi Fan, Claudia H T Tam, Emily W M Poon, Andrea O Y Luk, Alice P S Kong, Ronald C W Ma, Ele Ferrannini, Andrea Mari, Li Chen, Juliana C N Chan, Elaine Chow","doi":"10.2337/db24-1130","DOIUrl":null,"url":null,"abstract":"<p><strong>Article highlights: </strong>Dorzagliatin is a dual-acting allosteric glucokinase (GCK) activator that increases β-cell glucose sensitivity and second-phase insulin in GCK monogenic diabetes of the young. Actions of dorzagliatin on α- and β-cell function in normal and impaired glucose tolerance are unknown. In this study, dorzagliatin increased second-phase insulin in individuals with impaired glucose tolerance while suppressing glucagon in participants with normal glucose tolerance during a hyperglycemic clamp. With increasing glucose, plasma glucagon and total GLP-1 levels declined progressively. A modest to moderate positive correlation between glucagon and total GLP-1 was observed under both dorzagliatin and placebo treatments.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.\",\"authors\":\"Zhengli Bai, Ke Wang, Tiffany Yau, Cadmon K P Lim, Sandra T F Tsoi, Baoqi Fan, Claudia H T Tam, Emily W M Poon, Andrea O Y Luk, Alice P S Kong, Ronald C W Ma, Ele Ferrannini, Andrea Mari, Li Chen, Juliana C N Chan, Elaine Chow\",\"doi\":\"10.2337/db24-1130\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Article highlights: </strong>Dorzagliatin is a dual-acting allosteric glucokinase (GCK) activator that increases β-cell glucose sensitivity and second-phase insulin in GCK monogenic diabetes of the young. Actions of dorzagliatin on α- and β-cell function in normal and impaired glucose tolerance are unknown. In this study, dorzagliatin increased second-phase insulin in individuals with impaired glucose tolerance while suppressing glucagon in participants with normal glucose tolerance during a hyperglycemic clamp. With increasing glucose, plasma glucagon and total GLP-1 levels declined progressively. A modest to moderate positive correlation between glucagon and total GLP-1 was observed under both dorzagliatin and placebo treatments.</p>\",\"PeriodicalId\":93977,\"journal\":{\"name\":\"Diabetes\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-1130\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db24-1130","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.
Article highlights: Dorzagliatin is a dual-acting allosteric glucokinase (GCK) activator that increases β-cell glucose sensitivity and second-phase insulin in GCK monogenic diabetes of the young. Actions of dorzagliatin on α- and β-cell function in normal and impaired glucose tolerance are unknown. In this study, dorzagliatin increased second-phase insulin in individuals with impaired glucose tolerance while suppressing glucagon in participants with normal glucose tolerance during a hyperglycemic clamp. With increasing glucose, plasma glucagon and total GLP-1 levels declined progressively. A modest to moderate positive correlation between glucagon and total GLP-1 was observed under both dorzagliatin and placebo treatments.
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