mechanism to induce insulin resistance & reversal?
I've listened to Gerald Schulman's Banning lecture and your interview with him, both, several times. Fascinating and very informative- thank you for that. It appears that muscular insulin resistance involves a malfunction of the GLUT4 transport. Question 1: how does this malfunction come about? Stated differently, how does one develop muscular insulin resistance. As I remember all Schulman says about it is that the GLUT4 malfunction is "mediated by intracellular lipids." He didn't elaborate. I take that to mean that high concentrations of serum triglycerides leads to high concentrations of intracellular diglycerides and then the GLUT4 malfunction. Is this approximately correct? But if this is true why doesn't a reduction in serum triglycerides restore the functioning of the GLUT4 transfer mechanism?
what do you mean by "reversal of insulin resistance?"
In AMA17 you talk about the reversal of insulin resistance and give a clinical example. The intervention was Metformin, a low carb diet and an exercise regime. At six months there was an impressive improvement in pertinent labs (triglycerides, hdl and ALT). Now, that is nothing to scoff at clinically, but is this evidence of reversal of insulin resistance? The low carb diet will reduce or eliminate the need for insulin to clear glucose. The Metformin and exercise will reduce or bypass the GLUT4 transport malfunction. But have you returned the patient to normal insulin sensitivity; the healthy ability to clear glucose by muscular uptake? Doesn't seem so. What happens if the patient is returned to a "normal" diet with, say, 40% carbs and the Metformin is stopped? Will in insulin resistance return? Most likely. The clinical intervention is successful- but does this amount to the reversal of insulin resistance?