| Description: |
Purpose: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP76 2/2 mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP76 2/2 mice. Research Design and Methods: Blood glucose (BG) and lipid measurements were performed in RLIP76 +/+ and RLIP76 2/2 mice, using Ascensia Elite GlucometerH for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARc and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARa, PPARc, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. Results: The concomitant activation of AMPK and PPARc by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP76 2/2 mice, is a salient finding of our studies. The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARc and AMPK. Conclusions/Significance: All four drugs, rosiglitazone, metformin, gemfibrozil and atorvastatin failed to affect glucose and |