BP Figure 3: Chronic attenuation in blood glucose lowering by AZD1656 in the P446L mouse despite sustained islet GK staining.

Experimental details were as in Figure 1. A) Similar blood glucose by genotype at the start (0 wk) of the 20 wk study and sustained blood glucose lowering by AZD1656 (3mg/kg) after 19 wk compared to 2 wk in wild-type (PP) but not in LL mice. B) Difference (delta ∆) in blood glucose by AZD1656 treatment after 2 wk (white stripe) and 19 wk (grey stripe) relative to start of study (0 wk) showing lower efficacy at 19 wk in LL mice. C) Lack of effect of AZD1656 on plasma insulin. D) Glucose tolerance test after 2h food withdrawal determined at 18wk: glucose excursion and area under the curve (AUC). E) Representative immunostaining of pancreas for insulin, glucagon and GK after 20 wk HFHSD -/+ AZD1656 in PP and LL mice. F) Pancreatic islet % area determined from insulin staining. G) Islet GK-staining intensity showing higher intensity by AZD1656 treatment in wild-type, PP mice. *P < 0.005 effect of AZD1656; #P < 0.05 effect of genotype; $P < 0.01; $$ P< 0.005 19 wk versus 2 wk.