Wednesday, December 22, 2010

Hepatokines

Most of us have heard of cytokines, signaling molecules secreted by cells that affect other cells. Examples are the various interleukins, some of which stimulate inflammation and others of which reduce inflammation. They are like text messages between cells.

When some cellular stress occurs, let's say an infection in your finger, certain cytokines are the distress signals, telling other types of cells to rush to the site and fix it. Then when things seem to be OK, different cytokines tell the cells to cool it, to stop trying to fix things (fixing involves inflammation) and let the site get back to normal.

Fat cells used to be considered boring blobs of stored calories, with no interesting functions. Then they discovered that fat cells also secreted signaling molecules, which they termed
adipokines. One of the most widely known adipokine is leptin.

Hormones are also signaling molecules, and some people debate about which signaling molecules should be called cytokines or adipokines and which should be called hormones. Traditionally, hormones were considered to be molecules secreted by one organ that affected other organs. For example, beta cells secrete insulin, which has effects all over the body.

Cytokines were considered to be hormonelike molecules secreted by numerous cells throughout the body that affected immune system cells. Adipokines were considered to be hormonelike molecules secreted by fat cells. In both cases, a certain type of cell rather than a certain organ secretes the signaling molecules. And unlike hormones, which are usually synthesized and then stored within the cell for rapid release when needed, cytokines tend to be synthesized only when needed.

But there's a lot of overlap between cytokines and hormones, and some people think it's time to stop trying to classify the numerous new signaling molecules that seem to be discovered every week. The important thing is what they do.

Recently a new type of cellular "kine" has been proposed: the
hepatokine.

A protein called
selenoprotein P is produced in the liver and transports the trace mineral selenium from the liver to the cells that need it. These researchers found that selenoprotein P concentrations are higher in people with type 2 diabetes than they are in healthy people, and they proposed that overproduction of selenoprotein P in the liver causes insulin resistance and type 2 diabetes. Their research results were consistent with this hypothesis.

Interestingly, their results suggested that selenoprotein P works via AMPK, which is also affected by the diabetes drug metformin.

They said their research "raises the possibility that the liver functions as an endocrine organ by producing a variety of hepatokines and that the dysregulation or impairment of hepatokine production might contribute to the development of various diseases."

Whether or not selenoprotein P turns out to be vital in causing type 2 diabetes, I find this paper fascinating because it gives us a new way of approaching diabetes: looking for important modulators in a new place. Sometimes takes a shakeup of traditional ideas in order to make breakthroughs.

If there are adipokines and hepatokines, might there not also be musculokines or myokines? Skelatokines or osteokines? Or other "kines" in places no one has thought to look?

Maybe the tongue produces signaling molecules when it tastes different kinds of foods. We know that the sight, smell, and even thought of food can trigger nervous signals that affect gastric and insulin secretion (the cephalic phase of digestion). Why not small molecules as well?

Progress in genetic research is proceeding rapidly, but we still don't know what really causes type 2 diabetes. Perhaps these new ideas will stimulate new research that will come up with something that will help us prevent this epidemic disease.

2 comments:

  1. Very interesting! I've been intrigued by the idea that obesity is related to liver problems for a while, particularly after reading this by Peter@HyperLipid.

    http://high-fat-nutrition.blogspot.com/2010/03/getting-fat-is-good-official.html

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  2. I also think that not enough attention is being paid to glucagon. So much we don't know!

    And of course different people may have defects in different places.

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