Glucose is absorbed through the small intestine into the blood.

All glucose is taken into cells via hexose transporters: this is facilitated diffusion (no ATP).  Facilitated diffusion is passive diffusion through a channel made by a transmembrane protein; the proteins are able to open and close this channel. There are many ways channels can be opened/closed: ligand gated (i.e. neurotransmitter receptors), voltage gated (neurons), or, in the case of hydrophilic molecules such as glucose, mechanically gated: the channel is shaped like a closed "V".  Glucose goes to the bottom of the V, causes a conformational change and the "V" opens, but closes at the top (makes an upside down "V".)  Glucose can pass, and the V recloses.  All diffusion is down a concentration gradient.

The hexose transporters are called, randomly, "Glucose transporters 1-5" (GLUT1-5).

GLUT4 is the main transporter in muscle, fat, and the heart.  GLUT4 is insulin-sensitive (though it can also be activated by muscle contraction-- go figure.) In the absence of insulin, GLUT4s are stored in cytomplasmic vesicles floating around in the cytosol.  If insulin binds to the insulin receptor (an ATP dependent tyrosine kinase receptor-- NOT the GLUT4), a signal cascade is activated that causes the cytpolasmic vesicle to go to and bind to the plasma membrane and lodge the GLUT4 there. The GLUT4 then allows glucose to diffuse through.  When insulin disappears, the insulin receptor reconforms, the signal cascade stops, and the GLUT4 pinches off (by clathrin and other contracting proteins in the cell membrane) into a vesicle again (pinocytosis).

Thus, if there is no insulin: even if there is much glucose, there is no signal for the vesicle to go to the plasma membrane and lodge the GLUT4, so there will be no transport of glucose into the cell; so glucose stays high in the blood.  Thus we have Type 1 diabetes.


Insulin also stimulates the creation of glycogen in the liver and muscle.  [Insulin activates hexokinase (1st enzyme in glycolysis) as well as phosphofructokinase and glycogen synthase) and inhibits glucose-6-phosphatase ((opposite direction of hexokinase, same reaction) gluconeogenesis).]

Insulin promotes fatty acid synthesis.
Once glycogen synthesis has maxed out (i.e. about 30g, about 20% of the carbohydrate part of a studied meal, max in 4-6hrs,) then fatty acid synthesis IN THE LIVER takes over.  Glucose is converted to free fatty acids (FFAs) and dumped back into the blood as lipoproteins-- which are then broken up into FFAs.

FFAs go into the adipose cells of the body.  Glucose also goes into adipose cells-- via GLUT-- and are converted into glycerols.  Glycerol+FFAs= triglycerides.

Thus, insulin's role is to store fat and/or oxidize glucose.  Too little insulin will also trigger protein catabolism.

GLUT1 and GLUT3 account for 95% of the glucose transport to the brain. GLUT1 is for the blood brain barrier (the tight junctuions of the BBB are what require these channels), and GLUT3 is in the neurons. (pic here)  GLUT1 is also found in muscle.

These are not insulin dependent (like GLUT4 is) so the brain can continue to get its energy.  Not only does the distribution of GLUT 1 and 3 mirror capillary density and areas of relative glucose utilization, the GLUT1/3 densities can change depending on chronically increased (or decreased) need for glucose.  Interestingly, nicotine, which increases brain glucose utilization, increases GLUT1/3 but not capillary density.


GLUT2 and 7 are in the liver.  GLUT2 can also carry D-fructose.

GLUT5 is in the intestine, and some glial cells of the brain.

Type II diabetes is insulin resistance, not lack of insulin.  There is not, at least initially, a problem with the pancreas's secretion of insulin in response to high glucose.  The problem is at the level of the insulin receptor and/or GLUT, which become insensitive to the effects of insulin-- because there has been so much of it for so long. (For more info, see: News Physiol Sci. 2001 Apr;16:71-6.

Next up: how do antipsychotics affect glucose/insulin/transporters? 

(For a review: What We Know About Facilitative Glucose Transporters )