<b>Effects of dorzagliatin, a glucokinase activator, on α and β- cell function in individuals with impaired and normal glucose tolerance</b> Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.2337/figshare.29829494
· OA: W4413940102
<p dir="ltr">Dorzagliatin is a dual-acting allosteric activator of glucokinase (GCK). Dorzagliatin improved second-phase insulin secretion in individuals with type 2 diabetes and heterozygous carriers of GCK mutations. We investigated the effects of dorzagliatin on pancreatic insulin, glucagon and glucagon-like-peptide 1 (GLP-1) secretion in individuals with impaired glucose tolerance (IGT) and <a href="" target="_blank">normal glucose tolerance </a>(NGT).</p><p dir="ltr">In a double-blind, randomized cross-over, single-dose study, 9 participants with IGT and 10 with NGT underwent 2-hour 12 mmol/L hyperglycemic clamp following a single dose of dorzagliatin 50 mg or matched placebo. Plasma insulin, C-peptide, glucagon, total GLP-1 were measured at regular intervals.</p><p dir="ltr">There were no differences in first-phase insulin following dorzagliatin in either group. Dorzagliatin significantly increased second-phase insulin secretion rate and <a href="" target="_blank">β-cell glucose sensitivity</a> by 1.3-fold compared to placebo in IGT but remained similar in NGT. Dorzagliatin increased basal plasma insulin in the NGT group only. Glucagon (Area-under-the-curve <sub>0-120min</sub> 161±58 vs. 234±70 pmol*min/L, <i>P</i> = 0.01) was suppressed after dorzagliatin in NGT, but not the IGT group. Plasma glucagon was positively correlated with total GLP-1 levels. Dorzagliatin did not affect insulin sensitivity in either subject group.</p><p dir="ltr">Dorzagliatin has different actions on β and α-cells depending on glucose tolerance, increasing second-phase insulin secretion in IGT while enhancing glucose-suppression of glucagon secretion in NGT.</p>
