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BP Figure 6: AZD1656 increased liver GK activity in the <i>Gckr</i><sup><em>del/wt</em></sup><i> </i>mouse.

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posted on 2024-08-22, 14:14 authored by Brian FordBrian Ford, Loranne AgiusLoranne Agius
<p dir="ltr"><i>Gckr</i><sup>wt/wt</sup> and <i>Gckr</i><sup>del/wt</sup> were fed on a HFD without (open bar) or with (shaded bar) 3 mg/kg AZD1656 for 16 wk. A) Representative liver GKRP immunostaining of <i>Gckr</i><sup>wt/wt</sup>, <i>Gckr</i><sup>del/wt</sup> and <i>Gckr</i><sup>del/del</sup> genotypes on regular diet. B) Body weight after 16 wk on HFD -/+ AZD1656. C) Representative liver immunostaining for GKRP and GK at the end of the study on HFD -/+ 3 AZD1656. D) GKRP N-H scores; GK N-H scores, GK C-H scores and GK N-H/C-H ratio showing lower GKRP and GK nuclear staining and greater cytoplasmic GK distribution by del/wt genotype. E) GKRP-immunoactivity by Western blot showing more modest GKRP deficiency in del/wt genotype (30%) than in LL (80%) genotype. F) GKRP and GK immunoactivity after 16 wk study in <i>Gckr</i><sup>wt/wt</sup> showing an increase in GK / GKRP immunoactivity ratio by AZD1656 treatment. G) GKRP and GK immunoactivity after 16 wk study in <i>Gckr</i><sup>del/wt</sup> mice showing an increase in GK and GK / GKRP immunoactivity ratio by AZD1656 treatment. H) Lower liver GK activity in the Gckrdel/wt mice and increase by AZD1656 treatment. *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

Medical Research Council

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