Selenium induced glutathione peroxidase generation

TLDR: excess selenium induces excess glutathione peroxidase which blunts physiological superoxide/H2O2 signalling within a cell. This, as you might expect, is a Bad Thing.

I stumbled across this paper quite by accident. It has a number of problems, not least of which is that none of the authors appears to be a native english speaker and this tends to show through. It also carries a rather catastrophic typo/brain fart in the abstract, where TCA, as in tricarboxylic acid cycle, was written out in full as trichloroacetic acid cycle. Ouch. Never the less, they don't seem to like antioxidants.

High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS

Over all they don't seem to like suppressing the physiological levels of ROS needed for insulin signalling, certainly while feeding their rats a high carbohydrate diet. Not that they tell us what they fed the rats on!

This is the intraperitoneal glucose tolerance test result, look at "control" and "Se" for the effect of the high selenium diet:

Among many of the problems with the paper another is the difficulty distinguishing which line is which on the graphs. I think we can say the top line is clearly the selenium supplemented group and the bottom line is probably the control group. The main effect is at the 30 minute mark. This suggests to me that there is an inadequate first phase insulin response (needing ROS from RET induced by mtG3Pdh) to overcome the systemic failure of insulin action (also needing ROS from RET via mtG3Pdh to diffuse as far as the insulin receptor). By 60 minutes the difference is negligible. Had they measured insulin I'd bet the second phase response was exaggerated.

Here is the intraperitoneal insulin tolerance test result:

This time the bottom line is clearly the control group, top line the selenium treated group. From the control group I see no suggestion that this particular dose of insulin is inducing insulin-induced insulin resistance, so all we see is the failure of the insulin signalling activating action of ROS at the two hour mark. Note the lines are all parallel until the one hour mark. This is what suggests that there is nothing wrong with insulin action per se at the 30 minute mark and is another factor which makes me suspect that there is a failure to secrete insulin during the early stages of the IPGTT. The normal response to exogenous insulin, up until one hour mark, occurs while ever the exogenous insulin can overcome the loss of ROS caused by the glutathione peroxidase excess induced by the high selenium diet.

As humans we deal with huge numbers of xenobiotic antioxidants, mostly from plants. For the vast majority we can simply use our liver and/or kidneys to dump them to where they can do us no harm. Just occasionally we fail, as with selenium. The end result is not pretty.

Peter

There are some more interesting finings in the paper which might be worth chatting about. Maybe another day.

Random throw-away thought: Is this how uric acid induces insulin resistance? By being too good an antioxidant???? Hmmmmmm.