insulin and IGF-I, health,

[Guest guest]

Just a synopsis of IGF-1 from Hadley's endocrinology. (a monogram-ha)

Hadley describes IGF-I as a molecule that resembles insulin to which has been added amino acids (pg 259). He suggests the two evolved from a common molecule that performs the two functions: the metabolic function of insulin and the growth function of IGF-I.

It is certain that without IGF-I, humans are smaller (dwarfism) and too much results in gigantism. (pg 263,4). Pygmies, eg, express lower levels of IGF-I. (IGF-II does not seem to be involved in growth.)

Some cells have insulin receptors and some cells have IGF-1 receptors. Because the molecules are similar, both can share receptors. "Insulin is more potent in stimulating metabolic effects than IGF-I and IGF-II. On the other hand, insulin is less potent stimulating cell proliferation than {IGF-I and IGF-II}."

Pituitary ->somatotropin (STH) -> Liver, other tissues -> somatomedins, IGF-I, IGF-II

Somatomedin hypothesis: STH stimulates chondrogenesis by way of somatomedins. STH, not IGF-I, stimulates the multiplication of slowly cycling cells. IGF-I acts on the proliferation of the resulting chondrocytes.

Feedback control:

Pg 262 shows the control from CNS to the hypothalmus which releases somatocrinin(+) and somatostatin (-) to cause the pituitary to release STH.

Feedback control: (pg 261)

IGF-I stimulates hypothalmic somatostatin release and inhibits pituitary STH release.

My take:

If you believe the growth system stays intact, then IGF-1 is lower for smaller people and falls at age because of less requirement for bone growth. I suspect driven by some sympathetic nervous system feedback to the brain.

If I believe the parts fail due to aging or disease, and I'm sure they must in some cases, IGF-I might be lower because of less STH, or liver function failure, but other tissues can generate IGF-I.

OTOH, higher levels than required at age, might be due to failure of the feedback control systems.

Pygmies don't live longer.

So what are the cancer implications?

Look at:

http://tinyurl.com/8caln

http://jcem.endojournals.org/cgi/content/abstract/73/2/401?maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT=1 & author2=cohen & title=Insulin-like+growth+ & andorexacttitle=phrase & andorexacttitleabs=and & andorexactfulltext=and & searchid=1125076434843_3264 & stored_search= & FIRSTINDEX=20 & sortspec=relevance

Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells

P Cohen, DM Peehl, G Lamson and RG Rosenfeld

And look at the ref articles below it. The abstracts indicate sorta the history of thought about IGFs, etc in relation to cancer, from 1996 to 2005.

It seems to me the emphasis shifted from IGF-I, to more complex things, like IGFBP, receptors.

starting with:

"A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment." PMID: 9438850

to:

Interrelation of Energy Intake, Body Size, and Physical Activity with Prostate Cancer in a Large Prospective Cohort Study

Although energy intake is known to be imperfectly measured by questionnaire, we observed a positive association between energy intake and metastatic or fatal prostate cancer among men who were leaner, more physically active, younger, and who had a family history of prostate cancer. Our observations suggest the testable hypothesis that the elevated risk of clinically important prostate cancer in men with a high energy intake may be attributable to certain metabolic profiles that favor enhanced growth factor production over an increase in adiposity.

including:

Physical Activity and the Risk of Prostate Cancer in The Netherlands Cohort Study, Results after 9.3 Years of Follow-up

Discussion: The results of this current study do not support the hypothesis that physical activity protects against prostate cancer in men.

Other implications?

The American Journal of CardiologyVolume 90 • Number 12 • December 15, 2002Effect of congestive heart failure on the insulin-like growth factor-1 system

"Our study shows that in an elderly population of patients hospitalized for CHF, there was a significant decrease in total IGF-1, a profound decrease in IGFBP-3, and a marked increase in circulating free IGF-1. The decrease in total IGF-1 was not present in patients who received angiotensin-converting enzyme inhibitors."