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Glut 4 Redux.

Posted Jul 16 2009 10:46pm

The problem with being a know-it-all is that other people assume (not surprisingly) that you know it all.  Then, when a particularly bright (and well-researched) client says something like this:

I think modulation of the GLUT4 transporter is probably the key to the whole insulin sensitivity issue post exercise.  What do you think?

…you can only shrug your shoulders and say, “Gee, Gary, I don’t know…but I’ll get back to you on that.”

Have no idea what he was talking about?  Me either - until an hour ago.

What the heck is GLUT4 and why were we talking about it in the first place (read: killing time before the last exercise)?

First, some background.  You might recall me discussing the mechanism of insulin resistance, but here’s a quick catch-up:

Insulin functions to pull glucose (sugar) out of the bloodstream and into cells to be burned for energy or stored as glycogen (or to be stored as fat, if glycogen stores are already full).  Chronic high levels of insulin (caused by chronic high sugar intake) cause cells to become less responsive to insulin’s actions; in other words, cells stop responding to insulin and it becomes increasingly difficult to pull sugar out of the bloodstream and into the cells.  You body tries to compensate for this by increasing the amount of insulin (effectively “forcefeeding” sugar into the cells), but over time this strong-arming tactic grows less and less effective.  This process of insulin resistance eventually escalates into Type 2 Diabetes.

Conversely, being insulin sensitive is a good thing.  That means that it doesn’t require a whole mess of insulin to pull sugar out of your bloodstream.  Insulin sensitivity is strongly associated with longevity, which means you live longer if you’re more insulin sensitive.  Sounds good to me.

Ok, background established.  Now we’re about to wade into some deeper waters.  Tally ho!

Back to GLUT4:  GLUT4 is a sugar transporter protein that acts to “open the doors” for glucose (sugar) to enter cells.  There are 12 other sugar transport proteins, but the fourth isoform (GLUT4) is the main actor in glucose transport.

Let’s look at the insulin pathway a little more deeply here (thanks Wikipedia for a metabolic pathway diagram that isn’t intimidatingly offputting ):

This diagram illustrates simply and clearly the process of glucose entering a cell.  Insulin binds to its receptor site and sets off a chemical cascade that activates GLUT4.  GLUT4 opens the doors, and glucose is allowed into the cell, where it meets one of three fates: Glycogenesis, glycolysis, or lipogenesis.

Straightforward and neat.  But there’s an exception: The post-workout period.

The post -workout period is special, because during this time, you’re as insulin sensitive as you can get (makes sense, since your body is attempting to replenish its fuel stores as quickly as possible during this period, let’s let as much glucose through the doors as is possible; fill ‘er up!).  Here’s a nifty fact:  The exaggerated insulin sensitivity occurs via GLUT4, and doesn’t require the action ofinsulin.  What this means is that you’re literally bulletproof (sugarproof?) in the post-workout period, until glycogen stores are full (all fuel tanks have been replenished.  After that point, even a little spurt of insulin is enough to shift you towards fat storage; since, where else are you going to store all this extra sugar?

So let’s distill that into Cliffs Notes:

You exercise, intensely.  By doing so you deplete muscle and liver glycogen (stored sugar), burning it for energy.  After exercise, you decide to eat a 5 pound bag of potatoes.  The starch in the potatoes gets broken down into its constituent parts, namely glucose - sugar.  GLUT4 opens the doors to your cells and the sugar flows in, refilling muscle and liver cells with glycogen.  At the same time, your insulin levels rise, since the goal is to get that glucose into the cells as fast as possible.  Insulin rises, more GLUT4 is activated, more doors are opened, and soon enough your glycogen stores are full.  All that leftover sugar?  Repackaged as fat.

This clarifies post-workout reuptake for me a lot.  And, it answers a question I’d had for some time:

Insulin spikes retard growth hormone release.  Growth hormone is required for synthesis of new (and repair of damaged) muscle tissue.  And yet, a mix of carbs and protein (not just any carbs either, but readily digestible - simple - carbs) seems to work best in both replenishing muscle glycogen and in stimulating muscle tissue synthesis.  What gives?

Now I know what gives - GLUT4 allows for glucose influx independent of insulin.  So I guess you’re right, Gary.

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