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BP Figure 7: AZD1656 increases liver steatosis in the Gckrdel/wt mouse.

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posted on 2024-08-22, 14:14 authored by Brian FordBrian Ford, Loranne AgiusLoranne Agius

Gckrwt/wt and Gckrdel/wt 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 Gckrwt/wt and Gckrdel/wt mice. B) Higher plasma insulin by Gckrdel/wt genotype at 4 wk and 14 wk. C) Impaired glucose tolerance in AZD1656-treated Gckrdel/wt mice. D) Increased plasma FFA by AZD1656 treatment in Gckrdel/wt mice. E) Increased plasma cholesterol by AZD1656 treatment in Gckrdel/wt mice. F) Increased liver / body weight ratio by AZD1656 treatment in Gckrdel/wt mice. G) Increased liver triglyceride by AZD1656 treatment in Gckrdel/wt mice. H) Higher hepatocyte steatosis, microvesicular steatosis and fibrosis scores by AZD1656 treatment in Gckrdel/wt 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 RplpO showing increased expression of Fgf21, Cidea and Cidec by AZD1656 treatment in the Gckrdel/wt mice: n= 10 and 11 for Gckrwt/wt (-/+) and n= 6 and 10 for Gckrdel/wt (-/+) *P < 0.05 effect of AZD1656; #P < 0.05 effect of genotype.

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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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