Boost Height with Insulin

Insulin acts through the PI3K pathway to increase cellular proliferation and differentiation.  Leptin, Ghrelin, and Insulin would seem to not synergistic with each other but you can alter these levels by chemical and physical means.  Can altering Insulin levels and Insulin sensitivty(like IRS-1 which maintains the proper rate of bone turnover) boost height? 

Insulin Resistance Secondary to a High-Fat Diet Stimulates Longitudinal Bone Growth and Growth Plate Chondrogenesis in Mice. 

"It is known that overweight children are often more insulin resistant and taller than normal-weight peers. Because it has been hypothesized that insulin is implicated in the obesity-associated growth acceleration, we aimed to determine whether insulin resistance and secondary hyperinsulinemia are the causative mechanisms of such growth acceleration. Three-week-old mice were fed with standard chow or with a high-fat diet without or with daily administration of pioglitazone[a diabetic medication which reduces insulin resistance]. After 6 wk, high-fat mice' body and tibial growth, tibial growth plate height, and serum insulin were all greater than those of standard chow-fed mice. High-fat + pioglitazone mice were shorter, their tibial growth and the growth plate height reduced, and their insulin lower than those of high-fat mice. The addition of insulin to the culture medium of mouse metatarsal bones induced the metatarsal linear growth and increased the metatarsal growth plate height. In addition, insulin stimulated cultured chondrocyte proliferation and differentiation, with both effects being prevented by transfection with a small interfering RNA targeted to the insulin receptor. In conclusion, in high fat-fed mice, insulin resistance is causally related to accelerated skeletal growth. Our in vitro findings suggest that insulin may directly modulate skeletal growth by activating the insulin receptor directly at the growth plate." 

So it may not be Insulin that makes you taller but rather may insulin accelerates fusion via IRS-1 or other receptors.  Now we know that complete absence of IRS-1 will make you shorter but perhaps reducing the sensitivity of IRS-1 to insulin will result in you increasing in height.

"Pioglitazone is a synthetic ligand of the peroxisome-proliferator activated receptor-; by activating this receptor, it increases insulin sensitivity in the liver, fat, and skeletal muscle cells"

So Pioglitazone is a way to measure the effect of insulin sensitivity on height growth.  Mice who took a high fat diet with pioglitazone were shorter.


"No difference was found between PIO and control mice with respect to body weight gain, body cumulative growth, tibial growth, and growth plate morphology."

So in normal diet rats there was no effect of PIO meaning that PIO does not have height lowering effects independent of a high fat diet.

"In the high-fat + PIO mice, serum insulin level was significantly lower than that of high-fat mice, whereas no significant difference was detected between high-fat + PIO and high-fat mice or between high-fat + PIO and control mice relative to the serum IGF-I, leptin, IGFBP-1, IGFBP-3, testosterone, estradiol, FFA, and β-HB levels"

Insulin is what seems to exert the effects on height rather than related hormones.

"In the high-fat + PIO mice, the expression of phosphorylated-IR was weaker compared with the high-fat mice."

IR stands for insulin receptor.  Phosphorylated means it's inactivated.

"high-fat mice exhibited increased phosphorylated-IR expression"

High fat mice had more inactive insulin receptors in the growth plate.  IRS-1 is an example of an insulin receptor.

Likely what's happening is that the Insulin Receptors compete for insulin with something that increases height.  Insulin resistance allows for more serum levels of insulin available for other types of cells.  IRS-1 deficiency has been shown to be detrimental to height growth so it's unlikely that inactivation of insulin receptors is causing the height growth.

However....

"Our findings of the lack of any stimulatory effect of insulin on growth plate chondrocytes with a targeted silencing of the IR (and the persistent insulin stimulatory effects on chondrocytes with a targeted silencing of the IGF-IR) also support an IR-mediated regulatory role for insulin on skeletal growth and growth plate chondrogenesis."

Insulin does not have a stimulatory effect on chondrocytes apart from insulin receptors.  Maybe the effect of insulin could be on another cell type.

The role of insulin in chondrogenesis. 

"The ATDC5 chondrogenic cell line is typically induced to differentiate by exposure to insulin at high concentration[This can be bad as you want chondrocytes to proliferate for as long as possible] (10 microg/ml, approximately 1600 nM). Differentiation can also be induced by physiological concentrations of insulin-like growth factor-I (IGF-I). Unlike previous reports, we observed a stimulation of differentiation, as measured by collagen X expression and Alcian Blue staining for proteoglycan synthesis, upon exposure to insulin at concentrations (10-50 nM) consistent with signaling via the insulin receptor. Analysis of lysates from proliferating and hypertrophic ATDC5 cells demonstrated that exposure to 50 nM insulin induced tyrosine phosphorylation of insulin receptors but not IGF-I receptors or hybrid receptors. In contrast to the potent effects of IGF-I to stimulate both ATDC5 proliferation and differentiation, insulin was not as potent as IGF-I as a proliferating agent but more selectively a differentiating agent. Consistent with this result, insulin was less potent than IGF-I in inducing activation of the Erk1/Erk2 mitogenic signaling pathway. Furthermore, Erk pathway inhibition did not enhance the differentiating effects of insulin as it does in the case of IGF-I exposure. Extending our observations to fetal rat metatarsal explants, we observed significant stimulation of bone growth by 50 nM insulin. This could be accounted for by a disproportionate stimulatory effect on growth of the hypertrophic zone. The proliferative zone was not significantly affected. Based on our results in both ATDC5 cells and metatarsal explants, we conclude that the insulin functioning through insulin receptor has a dominant effect as an inducer of chondrocyte differentiation." 

This is consistent with the hypothesis that elevated levels of IRS-1 induce premature chondrocyte differentiation.  Organisms Transgenic in IRS-1 have shown enhanced hypertrophy in non-skeletal organs but the effect of transgenic IRS-1 one in bone really has to be studied separately as bone is unique in that premature differentiation of chondrocytes will result in reduced growth potential by shortening the proliferative phase. 

The High Fat +High Insulin Resistance Study was pretty recent so we'll have to watch to see for more details about how to manipulate insulin and insulin resistance for height gain. 

Let's look at some other functions of Insulin within the bone.

Novel functions for insulin in bone.

"The contemporary model assigns IGFs as central regulators of cell proliferation, survival, and organism growth, whereas insulin's action dominates at the level of regulation of fuel accumulation, storage[increased storage of water could encourage chondrogenic differentiation], and energy expenditure."

"leptin, an adipose-tissue-derived hormone that conveys critical information about peripheral energy storage and availability to the brain"<-Leptin can help you grow taller and Leptin also involves energy storage.  Remember that Leptin supplementation helps to reduce the height stunting effects of fasting.

"The skeleton is a highly metabolic tissue and is increasingly recognized as an important player in the coordination of global energy use through its hormonal interactions with other tissues"<-How to use this fact to increase height remains to be seen.

"osteoblasts express functional IR and respond to exogenous insulin by increasing bone anabolic markers, including collagen synthesis, alkaline phosphatase production, and glucose uptake"

No mention is made of chondrocytes, however chondrocytes can benefit from the same nutrient uptake, and this can increase height. 

Here's a study on insulin on human birth length:

Effects of cord serum insulin, IGF-II, IGFBP-2, IL-6 and cortisol concentrations on human birth weight and length: pilot study.

"The IGF system is recognised to be important for fetal growth. We previously described increased Insulin-like growth factor binding protein (IGFBP)-2 cord serum concentrations in intra-uterine growth retardation (IUGR) compared with appropriate for gestational age (AGA) newborns[decrease IGFBP-2 levels to grow taller], and a positive relationship of IGFBP-2 with Interleukin (IL)-6[IL-6 has positive height increasing effects it depends on whether those outweigh it's effects on IGFBP-2]. 
23 IUGR and 37 AGA subjects were followed up from the beginning of pregnancy, and were of comparable gestational age. Insulin, IGF-II, IGFBP-2, cortisol and IL-6 concentrations were assayed in cord serum at birth, and a multiple regression model was designed and applied to assess which were the significant biochemical determinants of birth size.
Insulin, cortisol, and IL-6, showed similar concentrations in IUGR and AGA as previously described, whereas IGF-II was lower, and IGFBP-2 increased in IUGR compared with AGA. IGF-II serum concentration was found to have a significant positive effect on both birth length (r:(:)0.546; p: 0.001) and weight (r:0.679; p: 0.0001). IGFBP-2 had a near significant negative effect on both birth weight (r:-0.342; p: 0.05) and length (r:-0.372; p:0.03)."

Insulin and cortisol did have a slight positive effect on birth length.

"Insulin increases IGFBP-2, and that IGFBP-2 was an independent predictor of insulin sensitivity."<-this could be why insulin resistance increases height. Lower IGFBP-2 levels.

"[There's] a positive effect of insulin placental concentration on both birth length and weight (unpublished), although the major effect would be mediated through cortisol placental concentration."

The increase in O-GlcNAc protein modification stimulates chondrogenic differentiation both in vitro and in vivo.

"Our aim was to investigate whether insulin-induced chondrocyte hypertrophy occurs through a modification in the amount of O-linked-N-acetylglucosamine (O-GlcNAc) modified proteins and in the expression of the key enzymes of this pathway: O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA). We also studied if O-GlcNAc accumulation per se, induced by an OGA inhibitor, was able to induce pre-hypertrophic chondrocyte differentiation both in vitro and in vivo. Insulin-induced differentiation of ATDC5 pre-chondrocytes occurred alongside with a gradual increase in the accumulation of O-GlcNac modified proteins (O-GlcNAcylated proteins), as well as an increase in the expression of OGT and OGA. In the absence of insulin, O-GlcNAc accumulation induced by thiamet-G, a specific OGA inhibitor, was able to increase the gene expression of differentiation markers, as well as the activity of MMP-2 and -9, although it was not able to induce proteoglycan accumulation. Thiamet-G also activated pERK, p-JNK and p-p38, and the O-GlcNAcylation of Akt. Thiamet-G administration to C57/bl mice induced a significant expansion in the growth plate height and in the hypertrophic zone height."

"The concentration of UDP-GlcNAc is regulated by glucose levels and is synthesized by the hexosamine biosynthesis pathway (HBP)"

"thiamet-G administration induces a significant increase in endochondral plate height, probably due to an increased length of the hypertrophic zone. However, we did not find this effect to be paralleled by an increase in tibial length. Based on our experiments, we were unable to determine whether a longer treatment with thiamet-G would induce an increase in tibial length."