<p dir="ltr"><i>Gckr</i><sup>wt/wt</sup> and <i>Gckr</i><sup>de</sup><sup>l/wt</sup> were fed on a HFD without (open bar) or with (shaded) 3 mg/kg AZD1656 for 16 wk. A) Lowering of blood glucose by AZD1656 after 4 wk and 14 wk in <i>Gckr</i><sup>wt/wt</sup> and <i>Gckr</i><sup>del/wt</sup> mice. B) Higher plasma insulin by <i>Gckr</i><sup>del/wt</sup> genotype at 4 wk and 14 wk. C) Impaired glucose tolerance in AZD1656-treated <i>Gckr</i><sup>del/wt</sup> mice. D) Increased plasma FFA by AZD1656 treatment in <i>Gckr</i><sup>del/wt</sup> mice. E) Increased plasma cholesterol by AZD1656 treatment in <i>Gckr</i><sup>del/wt</sup> mice. F) Increased liver / body weight ratio by AZD1656 treatment in <i>Gckr</i><sup>del/wt</sup> mice. G) Increased liver triglyceride by AZD1656 treatment in <i>Gckr</i><sup>del/wt</sup> mice. H) Higher hepatocyte steatosis, microvesicular steatosis and fibrosis scores by AZD1656 treatment in <i>Gckr</i><sup>del/wt</sup> mice. I) Representative haematoxylin and eosin (H&E) and Sirius red fast green (SRFG) images for histopathology scores, scale bar 200µm. J) Liver mRNA levels (RT-qPCR) for the genes indicated expressed as a ratio to <i>RplpO</i> showing increased expression of <i>Fgf21</i>, <i>Cidea</i> and <i>Cidec</i> by AZD1656 treatment in the <i>Gckr</i><sup>del/wt</sup> mice: n= 10 and 11 for <i>Gckr</i><sup>wt/wt</sup> (-/+) and n= 6 and 10 for <i>Gckr</i><sup>del/wt</sup> (-/+) *P < 0.05 effect of AZD1656; #P < 0.05 effect of genotype.</p>
Funding
MICA: Exploring a new perspective on the mechanism of action of Glucokinase Activators in liver, a preclinical study