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“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact”
~ Charles Darwin (it's evolutionary baybeee!)

Wednesday, November 17, 2010

Aspirin for Insulin Resistance? Part II: Not so fast

A follow-up post to a post a while back:  Aspirin for Insulin Resistance?

I just came across the following article that has me thinking "not so fast":   The effect of salicylates on insulin sensitivity

Although the carefully performed study by Kim et al. provides new insight into the mechanisms of fat-induced insulin resistance, we would like to caution against the preliminary conclusion concerning beneficial effects of salicylates on insulin resistance. First of all, in contrast to the findings of Kim et al. in the triglyceride (TG) infusion model in the rat, earlier studies in human volunteers using hyperglycemic clamp techniques reported increased insulin resistance by salicylate compounds (3,4). These findings suggest that the effects of salicylates may depend on the experimental model, and possibly on the species studied.....
The schematic below summarizes the various actions and possible impact on insulin sensitivity for salicylates, the text under this is the legend from the schematic.

The effects of salicylates on insulin resistance. There is significant overlap between the intracellular events induced by TGs (or FFAs) and TNF regarding the mechanisms of insulin resistance. Both stimuli activate IKK-β and decrease insulin-induced tyrosine phosphorylation of IRS-1; both increase intracellular ceramide concentrations, which leads to inhibition of Akt/protein kinase B activation and inhibition of GLUT-4 translocation. These effects induce a state of insulin resistance. The effects of salicylate compounds on these pathways may be divergent. That is, they may improve insulin resistance by blocking the activation of IKK-β (top), or they may worsen insulin resistance by inhibiting PG synthesis and thus potentiating TNF release (bottom). In addition, inhibition of PG will decrease synthesis of leptin, which is known to improve insulin sensitivity by stimulating IRS-1–associated PI 3-kinase activity. The beneficial effect of leptin on insulin action is thus decreased (bottom)
In conclusion, the influence of salicylate compounds on insulin sensitivity is multifactorial and involves both beneficial and deleterious effects. This should not preclude patients from taking low-dose aspirin to prevent cardiovascular disease (15), but more basal and clinical studies are needed before recommending higher dosages of salicylates for the treatment of type 2 diabetes itself.
Oh well.  Does make you kinda wonder what other meds might do.

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