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. 2010 Oct 18;285(52):40581–40592. doi: 10.1074/jbc.M110.176545

FIGURE 2.

FIGURE 2.

A and B, treatment improves glucose tolerance. Male, 22-week-old wild type mice fed with high fat for 16 weeks starting at 6 weeks of age showed significant improvement in intraperitoneal glucose (2 mg/kg) tolerance test (A) and glucose-stimulated insulin level during GTT (B). C and D, increased insulin sensitivity in the CDDO-Me-treated groups. C, insulin tolerance (1.5 units/kg, intraperitoneal) on Western diet-fed mice after 2 weeks of gavage treatment. Glucose level checked at 0, 15, 30, 60, and 120 min after insulin injection. D, represents the percentage blood glucose value. E–H, effect of CDDO-Me on glucose kinetics during hyperinsulinemic-euglycemic clamp. After 2 weeks of treatment, intravenous catheters were implanted surgically in the jugular vein of the mice, and the mice were allowed 4 days to recover. When the mice were able to access food and water freely, clamp studies were performed on these Western diet-fed mice using a continuous infusion of 10 milliunits/kg of body weight/min. E, basal glucose production rate (BGP) was not changed. F, glucose infusion rate (GIR) to maintain the euglycemic state was significantly higher in drug-treated mice. G, glucose disposal rate (GDR) was significantly increased. Solid bar, CDDO-Me; empty bar, control. H, glucose uptake was measured using 2-deoxy glucose under hyperinsulinemic-euglycemic clamp condition. Increased insulin-stimulated glucose transport activities were observed in isolated soleus and gastrocnemius muscles but not in epidymal fat tissue after CDDO-Me treatments in comparison with control mice. The data represent the means ± S.D. *, p < 0.05, control versus treated mice (n = 5 mice/group). I, Western blot of soleus muscle after clamp showed increased insulin signaling as detected by increased phosphotyrosine levels in CDDO-Me treated mice in comparison with vehicle-treated mice. Increased phosphorylation at tyrosine residue of IR, IRS1, IRS2, and p85 subunit of phosphatidylinositol 3-kinase, when immunoprecipitated with corresponding antibody in muscle sample after clamp, indicates insulin-stimulated glucose uptake by muscle. The corresponding bar graph shows quantification of the blot. The results are expressed as the means ± S.D. (n = 5 mice/group). *, p < 0.05, control versus CDDO-Me. IP, immunoprecipitation; IB, immunoblot.