Antagonism between type 1 and type 2 diabetes in unsaturated fatty acid biosynthesis

BRENNER RR

Future Lipidology

Año: 2006 vol. 1 p. 631 - 640

1746-0875

Diabetes mellitus type 1 characterized by a series of carbohydrate and lipid metabolism alterations due to the absence of insulin differs in many aspects from Diabetes mellitus type 2 in which, though the insulinemia is normal or increased, it is ineffective, provoking what is called “insulin resistance”. One of the different effects found is in the biosynthesis of unsaturated fatty acids, unsaturated acids that play outstanding roles in human health. Diabetes type 1 depresses the biosynthesis of all unsaturated acids of n-9, n-6 and n-3 series by depressing the mRNAs and activities of stearoyl-CoA desaturase-1 and D6 and D5 desaturases. Insulin promotes indirectly mRNAs transcription of the desaturases through SREBP-1c expression, and activation, process in which LXR is also involved. Desaturases are also modulated by nuclear receptors PPARs and RXR that are activated by unsaturated fatty acids. Diabetes mellitus type 2 that was investigated using a rat sucrose rich diet model and a spontaneous genetic rat model (eSS), evokes on the contrary an increase of hepatic desaturases mRNA transcription. This effect is found together with increased triglyceridemia, NEFA and insulinemia, but insulin enhancement is not the cause of desaturase increase. Troglitazone a thiazolidinedione agonist of PPAR-g1, depresses the hepatic desaturases mRNA, apparently by an indirect depression of hepatic PPAR-a evoked by a decrease of the free fatty acid flux to the liver. Therefore, both types of diabetes mellitus evoke antagonistic effects on the biosynthesis of unsaturated fatty acids by modification of enzymes actively modulated by the interaction of a complex system of mechanisms in which insulin, nuclear receptors and transcription factors are involved.