Author: Brenner, Rodolfo R

Source: Future Lipidology, Volume 1, Number 5, October 2006 , pp. 631-640(10)

Publisher: Future Medicine

Abstract:

Type 1 diabetes mellitus, which is characterized by a series of carbohydrate and lipid metabolism alterations due to the absence of insulin, differs in many aspects from Type 2 diabetes mellitus, in which, although insulinemia is normal or increased, insulin is ineffective, provoking what is termed insulin resistance. One of the differences observed regards the biosynthesis of unsaturated fatty acids, which play a variety of roles in human health. Type 1 diabetes depresses the biosynthesis of all unsaturated acids of the n-9, -6 and -3 series by depressing the mRNAs and activities of stearoyl-CoA desaturase-1 and Δ6 and Δ5 desaturases. Insulin indirectly promotes mRNA transcription of the desaturases through sterol response element-binding protein-1c expression and activation, a process in which liver X receptors are also involved. Desaturases are also modulated by nuclear receptors, peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors, which are activated by unsaturated fatty acids. By contrast, Type 2 diabetes mellitus, investigated using a rat sucrose-rich diet model and a spontaneous genetic rat model, evokes an increase in hepatic desaturase mRNA transcription. This effect is found together with increased triglyceridemia, nonesterified fatty acids and insulinemia, however, insulin enhancement is not the cause of the desaturase increase. Troglitazone, a thiazolidinedione agonist of PPARγ1, depresses the mRNA of hepatic desaturases, apparently by an indirect depression of hepatic PPARα 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 the modification of enzymes actively modulated by the interaction of a complex system of mechanisms in which insulin, nuclear receptors and transcription factors are involved.

Keywords: Δ5 desaturases; Δ6 desaturases; eicosanoids; liver X receptor; nuclear receptors; peroxisome proliferator-activated receptor; retinoid X receptor; stearoyl-CoA desaturase; sterol response element binding proteins-1c; transcription factors

Document Type: Research article

DOI: http://dx.doi.org/10.2217/17460875.1.5.631

Affiliations: 1: Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, Facultad de Ciencias Médicas, calles 60 y 120, 1900-La Plata, Argentina., Email: rbrenner@atlas.med.unlp.edu.ar

Publication date: 2006-10-01

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• Future Lipidology addresses therapeutic strategies and emerging topics in this complex area of cardiovascular medicine. The journal delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum.
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