S26948, a new specific peroxisome proliferator activated receptor gamma modulator improved in vivo hepatic insulin sensitivity in 48 h lipid infused rats.

Abstract	We examined whether S26948, a new specific peroxisome proliferator activated receptor gamma modulator prevented insulin-resistance induced by a 48 h intralipid-infusion in normal rat (IL rats). The effect of S26948 (30 mg/kg) was compared to rosiglitazone (10 mg/kg). Rats were catheterized in the right jugular vein 4 days before the beginning of the 48 h lipid or saline infusions. 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.
Authors	Kyung-Ah Kim Sohn, Céline Cruciani-Guglielmacci, Nadim Kassis, Laurence Clément, Fetta Ouali, Michèle Caüzac, Nicolas Lebègue, Pascal Berthelot, Daniel-Henri Caignard, Jean-Paul Pégorier, Pierre Renard, Catherine Dacquet, Alain Ktorza, Christophe Magnan, Consortium of the French Ministry of Research and Technology
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 608 Issue 1-3 Pg. 104-11 (Apr 17 2009) ISSN: 1879-0712 [Electronic] Netherlands
PMID	19250932 (Publication Type: Journal Article)
Chemical References	Adiponectin Benzothiazoles Blood Glucose Fatty Acids, Nonesterified Hypoglycemic Agents Insulin PPAR gamma S26948 Thiazolidinediones Rosiglitazone Heparin Glucose
Topics	Adiponectin (blood, metabolism) Animals Benzothiazoles Blood Glucose (metabolism) Cells, Cultured Cross-Over Studies Dose-Response Relationship, Drug Fatty Acids, Nonesterified (blood, metabolism) Gene Expression (drug effects) Gluconeogenesis (drug effects) Glucose (antagonists & inhibitors) Glucose Clamp Technique Heparin (pharmacology) Hepatocytes (drug effects, metabolism) Hypoglycemic Agents (metabolism, pharmacology) Infusions, Intravenous Insulin (metabolism, pharmacology) Insulin Resistance Liver (drug effects, metabolism) Male Oxidation-Reduction PPAR gamma (agonists, pharmacology) Random Allocation Rats Rats, Wistar Rosiglitazone Saphenous Vein Thiazolidinediones (pharmacology) Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!