American Diabetes Association
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Dorzagliatin, a dual-acting glucokinase activator, increases insulin secretion and glucose sensitivity in glucokinase-maturity-onset diabetes of the young (GCK-MODY) and recent-onset type 2 diabetes

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posted on 2022-10-28, 20:59 authored by Elaine Chow, Ke Wang, Cadmon KP Lim, Sandra TF Tsoi, Baoqi Fan, Emily Poon, Andrea OY Luk, Ronald CW Ma, Ele Ferrannini, Andrea Mari, Li Chen, Juliana CN Chan

Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is caused by heterozygous inactivating mutations in glucokinase (GK, gene symbol GCK) and impaired glucose sensing. We investigated effects of dorzagliatin, a novel allosteric GK activator, on insulin secretion rates (ISR) and beta-cell glucose-sensitivity (βCGS) in GCK-MODY and recent-onset type 2 diabetes. In a double-blind, randomized cross-over study, eight participants with GCK-MODY and 10 with type 2 diabetes underwent 2-hour 12-mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75mg or matched placebo. Effects of dorzagliatin on wild-type and mutant GK enzyme activity were investigated using a nicotinamide adenine dinucleotide phosphate (NADP+) coupled assay with glucose-6-phosphate dehydrogenase (G6PD) in vitro.

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The funder reviewed the protocol and final manuscript but had no role in the conceptualization, design, data collection, analysis, decision to publish or preparation of the manuscript.

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