Insulin desaturase activity effects

The effect of hormones on the A6 desaturation of linoleic, a-linolenic and oleic acids was shown as early as 1966 (Mercuri et al, 1966, 1967). It was found that alloxan diabetes depressed the A 6 desaturase activity of rat liver microsomes and insulin injection corrected the defect in less than 38 h. The simultaneous injection of actinomycin D or Puromycin that abolished protein synthesis imparted the reparative effect of insulin and suggested that insulin effect might involve A6 desaturase induction. However... 

Dietary changes that result in the induction of synthesis of fatty acid synthetase produce similar rises in activity of A9 desaturase but have little effect on A4, A5 or A6 desaturases. Several hormones have been reported to influence desaturase activity, notably insulin. In the rat, made diabetic by poisoning the pancreas with streptozotocin, liver A9 desaturase activity is low and can be restored by administration of insulin. However, dietary fructose, glycerol or saturated fatty acids can also restore enzyme activity, so that the role of insulin may be indirect. Little further progress can be made until purified desaturases are available so that short- and long-term regulation can be studied directly. 

Accumulating evidence indicates that SREBP-lc mediates the effect of insulin on transcriptional activation of genes involved in fatty acid synthesis (Horton et ah, 2002 Shimomura et al., 1999 Foretz et al., 1999). When mice are fed with a fat free high-carbohydrate diet, the liver SCD mRNA is induced about 50 fold (Ntambi, 1995 Sessler and Ntambi, 1998), however, the induction is blunted when SREBPl-c is disrupted. Because SDC and D6D mRNA expression were diminished in diabetic rats, and restored by insulin administration (Waters and Ntambi, 1994), the insulin effect on the desaturase genes is likely to be mediated by SREBP-lc. Studies with primary culture rat hepatocytes showed that the expression of a dominant negative SREBPl-c blocked the effect of insulin on the transcriptional activation of SCD, whereas expression of a dominant positive SREBPl-c mimicked the insulin effect (Foretz et al.,... 

The enzyme is sensitive to hormones concentration. Insulin enhance the reaction but the effect is eliminated by protein synthesis inhibition. Hyperglucemic hormones as glucagon, and epinephrine depress the activity of the A6 desaturase by reactions triggers by an increase of cAMP concentration. 

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