Animals were intraperitoneally injected once daily with vehicle, S26948 or rosiglitazone.
At the end of the infusion the rats underwent either a glucose tolerance test or a euglycemic-hyperinsulinemic clamp.
Finally isolation and incubation of hepatocytes in another series of rats were performed.
Intralipid infusion leads to a 4-fold increase in plasma free fatty acid concentration compared to controls (C). Both S26948 and rosiglitazone decreased plasma free fatty acid concentration in IL rats compared to vehicle treated IL rats. Glucose-induced insulin secretion was significantly increased in IL compared to C and was associated with insulin resistance.
Both S26948 and rosiglitazone treatments normalized glucose-induced insulin secretion and improved insulin action in IL rats. However, S26948 specifically improved hepatic insulin sensitivity whereas rosiglitazone improved both hepatic insulin sensitivity and insulin-stimulated glucose utilization. Finally, studies on isolated hepatocytes showed differential effect of both compounds on gene expression of key enzymes of glucose metabolism.
Our data show that non thiazolidinedione S26948 may represent an alternative way for the management of dysregulated hepatic insulin sensitivity.
JournalEuropean journal of pharmacology
Eur J Pharmacol (1879-0712)
University Paris Diderot, CNRS, Paris, France.
Eur J Pharmacol. 2009 Apr;608(1-3):104-11
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