ANTAGONISM OF DIABETES TYPE 1 AND DIABETES TYPE 2 ON THE TRANSCRIPTION AND ACTIVITY OF ENZYMES CONTROLLING UNSATURATED FATTY ACID BIOSYNTHESIS AND PPAR-ƒÑ AND PPAR-ƒ× EFFECTS

R.R. BRENNER; A.M. BERNASCONI; M.S. GONZÁLEZ; M.A. MONTANARO; S. MONTENEGRO; M.C. TARRÉS; S.M. MARTÍNEZ; Y.B.LOMBARDO; A. CHICCO; O.J. RIMOLDI

Corcega, Francia

Congreso; 46th Internationanal Conference on the Biosciences of Lipids; 2005

ICBL

ANTAGONISM OF DIABETES TYPE 1 AND DIABETES TYPE 2 ON THE TRANSCRIPTION AND ACTIVITY OF ENZYMES CONTROLLING UNSATURATED FATTY ACID BIOSYNTHESIS AND PPAR-a AND PPAR-g EFFECTS. R.R. Brennera, A.M. Bernasconia, M.S. Gonzáleza, M.A. Montanaroa, S. Montenegrob, M.C. Tarrésb, S.M. Martínezb, Y.B.Lombardoc, A. Chiccoc, O.J. Rimoldia. a.       INIBIOLP (CONICET-UNLP), La Plata, Argentina. b.      Cátedra de Biología, University of Rosario, Argentina. c.       Departmento de Ciencias Biológicas, Universidad del Litoral, Santa Fé, Argentina.   Diabetes Mellitus is a widespread disease that alters carbohydrate and lipid metabolism. Experimental streptozotocin diabetes type-1 evoked in the rat hypoinsulinemia, hyperglycemia and significant depressions of liver stearoyl-CoA desaturase-1(SCD-1), D6 desaturase and D5 desaturase mRNAs and activity that were normalized by insulin injection. Antagonistically two experimental rat models of diabetes type-2, showing an insulin resistance, represented by animals feeding a sucrose-rich diet or the spontaneously genetically altered eSS rats, showed hyperglycemia with normoinsulinemia, hypertriglyceridemia and hyper NEFA, but liver mRNAs and activities of SCD-1, D6 and D5 desaturases were enhanced. Troglitazone that enhances PPAR-g activity in adipose tissue when administered to rats receiving a high sucrose diet depressed the acidemia, normalizing other blood parameters without insulinemia changes and depressed the three hepatic desaturases mRNA and activity. Fenofibrate an agonist of hepatic PPAR-a activity increased mRNAs and activities of the three desaturases not only in insulin-treated diabetic type-1 rats but also, although less effectively, on diabetic rats without modifying the glycemia and insulinemia. The two drugs normalizing effects are explained respectively by an indirect free fatty acid- dependent and a direct agonistic action on PPAR-a hepatic activity that modulates per se the desaturases. In diabetic-type-1 rats the effect of insulin would be mainly evoked through the LXR-SREBP-1c mechanism, different, but synergic to the PPAR-a mechanism.