Thursday, 27 December 2012

Adipose GLUT4 Knockout

Well, not really knock-out, but a severe deficiency nonetheless, of GLUT4 only in the adipose tissue. I was after this paper to try and help me distinguish between the affects of insulin and glucose uptake into adipose tissue and how it might influence obesity.

From this model we learn that.....

  • In adipocytes, basal glucose uptake is reduced by 40%
  • In adipocytes, insulin-stimulated glucose uptake is reduced by 72%
  • Growth and body fatness are normal
  • Glucose transport into skeletal muscle is impaired by 40%, despite intact GLUT4's in muscle.
  • The ability of insulin to inhibit liver glucose production during hyperglycemia was 50% reduced.

So the surprising conclusion from this study is that reduced GLUT4's in adipocyte's gets you severe metabolic disturbances with insulin resistance in both skeletal muscle and liver. Contrast this to the FIRKO mouse however, that is metabolically healthy. This to me indicates that it is a reduction in this thing "basal" glucose uptake into adipocytes that is causing metabolic issues, and not a reduction in insulin-stimulated glucose uptake per se.

The basal glucose uptake is something important to note, I.E. , there is uptake of glucose into adipocytes even without insulin.

A possible link is "this" paper. In short, there is another serum protein, that is yet unidentified, that is also responsible for GLUT4 expression on adipocytes. This factor still functions in insulin resistance, and critically does not activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 expression.

OK OK, so where does all this stuff leave us anyway?

We also have to recall that overexpression of GLUT4 on adipocytes results in increased fat mass accompanied by gross adipocyte hyperplasia. Is there anyway to "over-express" GLUT4's on adipocytes without being a transgenic mutant? Ofcourse there is, its called INSULIN dummy. With all the above in hand, I can only conclude that it is insulin-stimulated glucose disposal into adipocytes that is a method of creating obesity. "Basal" glucose uptake into adipocytes, perhaps via this unidentified serum protein, appears to be both healthy and actually necessary for proper metabolic health.

No comments:

Post a Comment