From: Insulin Regulation of Human Hepatic Growth Hormone Receptors: Divergent Effects on Biosynthesis and Surface Translocation, Kin-Chuen Leung, Nathan Doyle, Mercedes Ballesteros, Michael J. Waters, And Ken K. Y. Ho, The Journal of Clinical Endocrinology & Metabolism 2000 Vol. 85 No. 12 4712-4720
In the study they recognized the importance of insulin and how it interacts with growth hormone, specifically highlighting that "insulin is essential for GH stimulation of IGF-I production and growth."
They then focused on the results of their study. They found that:
- Insulin up-regulated total and intracellular GH-receptors in a concentration-dependent manner.
- The abundance of GHR messenger ribonucleic acid and protein, ... respectively, markedly increased with insulin treatment.
[So the more insulin that was used the more biosynthesis or creation of GH-receptors that occurred. Now these receptors while abundant were not necessarily moved to the surface of the cell nor where they activated. Just a pool of GHRs was created.]
CAVEAT: Parts of the GH-Receptor can move to the nucleus and mediate gene expression. See the wonderful post that follows on "Growth Hormone Receptor structure, post-biogenesis behavior and degradation"
- It increased surface GHRs in a biphasic manner, with a peak response at 10 nmol/L, and modulated GH-induced Janus kinase-2 phosphorylation in parallel with expression of surface GHRs.
[So insulin increases the number of GH-receptors that make it to the cell surface AND increase the "intensity" of activation...but up to a point. After that point is reached insulin begins to hinder both the number of GH-receptors and "intensity" of activation"]
To quote from the study on this point:
Insulin induced a concentration-dependent increase in GHR biosynthesis, but simultaneously inhibited surface translocation. However, the net effect of reducing receptor surface availability only occurred at concentrations greater than 10 nmol/L, a concentration causing 70% inhibition of surface translocation. These data suggest that up-regulation of surface GHRs can occur with as little as 30% of intracellular receptors available for translocation to the cell surface. At concentrations above 10 nmol/L, the inhibitory effect of insulin on surface translocation overrides the compensatory effect of a 4- to 5-fold increase in receptor biosynthesis.
[So this means that insulin increases GH-receptors by 400-500% but that as insulin rises it reduces the number of those GH-receptors that make it to the surface and are active. There is a point at which insulin begins to reduce the benefit of this GH-receptor creation. That point is 10 nmol/L of insulin. Just prior to that point insulin has inhibited substantially the translocation of GH-Receptors but the increased quantity made up for it and created an overall net benefit.]
So the problem becomes how to translate that pivot point (10 nmol/L) into a number we can use.
From: Correspondence Letter Regarding Article by von Lewinski et al, "Insulin Causes [Ca2+]i-Dependent and [Ca2+]i-Independent Positive Inotropic Effects in Failing Human Myocardium", Chih-Hsueng Hsu, MD; Cheng-I Lin, PhD; Jeng Wei, MD, Circulation. 2005;112:e367
...we find that "3 IU/L, equivalent to 20 nmol/L" ...so 10 nmol/L is equivalent to 1.5 IU/L
From Wiki Answers
http://wiki.answers.com/Q/How_many_l...an_beings_have...we find that humans have 5-6 litres of blood in general.
So 5 x 1.5 = 7.5IU
So 6 x 1.5 = 9IU
Therefore the point at which the amount of insulin in plasma becomes a negative rather then a positive is approximately 7.5 to 9 IUs.
So to arrive at a net benefit an insulin amount below that threshold point such as 5-6 ius is desirabl
