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[A1CR]

[posted on behalf of CRON4healthyfuture]

Bartke's boys are closing in on the CR connection to IGF-1/insulin

http://dx.doi.org/10.1016/j.exger.2006.01.009

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You can right click it, and open it in a new browser window, to make this 2006 technology worky-worky....

The actual paper shows that these boys stepped in it bigtime. Welcome to the wonderful world of nonlinear biology.......follow the bouncing ball, if you can!

This is wild goose chase, one gene goes up because the other goes down, and vice versa........at this stage, biologists don't know how it all "fits together".....they aren't good enough at watching all the variables simultaneously, so there tends to be an overemphasis on individual variables that are amenable to the current technical limitations.

But, it's truth, and the truth is messy. In any case, their findings generally support the idea that insulinemic signals go down in the blood, and the receptors get upregulated at the organ level, and the internal signal mediator gene expression levels don't change in a "predictable manner".

This is where proteomic analysis is the future; are there phosphates on the proteins, or not? Are they acetylated, or not? Are there allosteric interactions of interest, or not?

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Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

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"In the present study, long-lived GHR/GHBP knockout (KO) mice have been subjected to long-term 30% CR. We have previously reported that this regimen of CR produces the expected reduction in body weight in both KO and normal mice (Al-Regaiey et al., 2005). In the same study, CR down regulated circulating IGF1 levels in normal animals, while the extremely low levels of circulating IGF1 in both KO-AL and KO-CR animals were below the detection limits of the employed ELISA kit used in these studies (Al-Regaiey et al., 2005). Moreover, CR significantly decreased blood glucose in both phenotypes, with no significant difference between KO and N mice fed ad libitum (N-AL 189.4±9.6, N-CR 139.7±14.1, KO-AL 155.0±14.1, and KO-CR 74.8±11.5 mg/dl) (Al-Regaiey et al., 2005). It was also shown that the insulin level was significantly decreased in normal and KO animals after CR, while KO-AL animals had the expected reduction of insulin as compared to N-AL mice. (N-AL 4.2±0.7, N-CR 1.4±0.2,
KO-AL
0.9±0.1, and KO-CR 0.4±0.1 ng/ml) (Al-Regaiey et al., 2005). The genotype (KO vs. N) and CR-induced increase in insulin sensitivity suggested by these findings was supported by the results of homeostasis model analysis (HOMA) (Masternak et al., 2005a). Studies in worms, flies and mice (including GHR-KO, Ames dwarfs and Snell dwarfs), as well as widely examined effects of CR in various animal species, strongly indicate insulin signaling as an important pathway in the control of aging (Tatar et al., 2003)."