[Lotus]

Change your receptors, change your set point

Receptor regulation.

Receptors are “message receivers” located throughout our bodies. They are typically transmembrane proteins located on the surfaces of cells, and they bind with hormones and neurotransmitters to “receive” the signal and initiate a sequence of changes in our bodies — often profound system-wide changes in energy utilization, tissue growth, or the perception of pleasure and pain. For some reason, receptors don’t get the public attention that gets showered on the communication chemicals — the hormones and neurotransmitters. And yet, as I shall argue, the receptors may be far more important than the signaling compounds that they interact with, because they do not change by the minute or hour, but are long-lasting parts of the control systems of our bodies. If hormones and neurotransmitters are the “software”, receptors are the “hardware”.

The key process to understand is called receptor regulation, the process which controls the number, location and sensitivity of receptors. There are two forms: upregulation (an increase in the number and/or sensitivity of receptors in each cell) and downregulation (the reverse process). Wikipedia explains downregulation by describing how insulin resistance develops in response to elevated insulin levels:

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell’s surface without doubts. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex. (Italics added by me for emphasis).

So not only are the insulin receptors drawn inside the cell (like a turtle into its shell); they are also actively digested and degraded, making them less available to readily redeploy when glucose and insulin levels drop again. New receptors are always being synthesized, but they are degraded more quickly than they can be replenished if insulin levels remain high. The resulting downregulation of insulin receptors forms the basis for the condition of insulin resistance, in which insulin at normal levels loses its ability to efficiently shuttle glucose from the bloodstream into liver, muscle, brain, adipose or other tissues; the body responds by further increasing insulin, resulting in a vicious cycle of hyperinsulinemia. Reversing this process — growing new insulin receptors — takes time and requires sustained periods with low circulating levels of insulin in order to foster the growth of new receptors.

It is quite revealing to look at how how receptor regulation can undermine “message control” treatments, due to the way the body adapts. Let’s take a look again at how this plays out in the above three examples of obesity, addiction, and depression:
http://gettingstronger.org/2010/10/chang...-setpoint/

Want to optimize your receptors?, read the article....