DOM FIGURE 4 Improved ATP homeostasis and attenuated ChREBP target gene induction after 4 week or 8 week treatment with AZD1656.
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C57BL/6 mice were treated for either 4-wk (A-H) or 8-wk (I-P) without (0) or with AZD1656 (1 or 3mg/kg body wt) and used for the studies in Fig. 3E-H before they were euthanized for hepatocyte isolation. After overnight culture of hepatocytes, parallel incubations were performed in MEM with the substrates indicated (see legend to Fig. 2 for 4-wk treatments) for either 1h for determination of G6P, G3P, ATP (A-D,I-L) or 4h for mRNA analysis of the indicated genes (E-H,M-P). E,M: Basal mRNA levels at 5mM glucose normalized to vehicle 5mM glucose; F-H,N-P, mRNA levels of the indicated genes as % respective controls at 5mM glucose. Means ± SEM, n= 3-5 (4-wk, A-H) or n=4 (8-wk, I-P), *P< 0.05 vs respective control (5G); # P < 0.05 vs respective untreated (0 mg/kg).
MICA: Exploring a new perspective on the mechanism of action of Glucokinase Activators in liver, a preclinical study
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