Hepatic extraction of fructose

EDIT on 2nd March 2011. This post is incorrect! I'll leave it up as a reminder to myself to check all facts, even when net access is very limited. The pancreas monitors enteric glucose hormonally, not by direct access to the portal vein blood flow. It gets as much or as little fructose exposure as any organ than the liver. Mea culpa. The links are good, so the post has some use still. Thanks to Kurt for catching this one for me. END EDIT



OK, still no posting except for this brief note which is only delivered because the clocks changed, Daniel had a disturbed night and we both have been wake for several hours. Another heavy clinical week to come as of tomorrow... I publish the non-viagra comments on older posts by a brief mouse click but still don't get time to comment back and that will probably apply to this post too. That's just how it is at the moment. Tee hee, probably means there are a ton(ne) of typos in this post too!



Over the last few months I've tried to keep up with my favourite blogs (difficult because work blocks access to all blogs). Many people commented on the fructose and cancer article via Reuters. I'd just like to stick a few observations down about it and about hepatic fructose extraction.

Don over at Primal Wisdom has a nice post discussing the subject and its possible implications. But does fructose feed cancer in vivo? Does it even get to any cancer cells outside the liver and gut?

This led to a follow on post about hepatic fructose extraction, with a nice paper from Japan in Diabetes Care cited. It's unfortunate that ref 11 and ref 13 from this article are both unavailable, even in abstract form. One title specifies investigation of splanchnic blood levels of fructose, which is a very vague term but might include portal vein from gut to liver and might just, if we were lucky, include hepatic vein concentrations, which would allow us to see hepatic extraction rate and systemic penetration.

This would be nice as the second reference's title only seems to specify the role of the liver in the mop-up following intravenous fructose administration. Obviously intravenous fructose bypasses hepatic extraction, so it might not say too much about dietary fructose penetration in to the systemic circulation.

When we look at the micro molar concentrations of fructose (as opposed to milli molar for glucose) in serum as measured in DC article we are looking at venous samples. If the fructose in these samples has come from the diet in the gut it will have been fructose extracted by the liver, then pumped around the body, been fructose extracted by the tissues and only then finally arrived at the sampling needle. It looks like an open question how much fructose comes past the liver and hits the tissues themselves, to feed cancer cells.

You might get more information by measuring the arterial concentration of fructose, as opposed to the venous concentration. Arterial concentration is the hepatic vein fructose diluted in the the full venous return/cardiac output. This would give an indication of hepatic fructose passage without the complication of tissue extraction. But you can't have what's not in the paper and arterial blood samples are a little harder to obtain than venous samples!

EDIT: Cynthia found the abstract to the rat paper. Hepatic extraction is around 50-70%, this dilutes in the venous return but there is still a significant surge through the systemic circulation. This is particularly interesting as humans do metabolise fructose in their muscles, which might just have something to do with systemic as well as hepatic insulin resistance from fructose. I wish I had the time to follow these leads. Abstract text in the first comment. Ta Cynthia. END EDIT

The DC paper does suggest, among several explanations, that the higher venous fructose in diabetics might come from glucose via the polyol pathway. Glucose to sorbitol, sorbitol to fructose. This endogenously generated fructose then drops in to the venous system and gets sampled before going off to liver and/or muscles for metabolism.

So there are a lot of "if"s, "but"s and "maybe"s.

However, the cancer feeding effect of fructose was noted in pancreatic cells. Pancreatic cells sit in the portal vein to monitor gut glucose absorption. They also get hit by the full load of fructose arriving after a couple of cans of soda. It doesn't matter how much fructose the liver extracts if you happen to be a pancreatic cell sitting in the portal blood flow.

You get nuked.

If you are a pancreatic cancer cell you get fed.

Peter

BTW NAFLD has it's parallel in non alcoholic fatty pancreatic disease. Both go from normal through fatty infiltration to chronic inflammation to scarring to neoplasia. Both organs sit in the portal venous drainage from the gut. Another few posts there but...