Instestinal growth through growth factor pathways...

[soulstealer]

GH elevates serum IGF-I levels but does not alter mucosal atrophy in parenterally fed rats

C. A. Peterson, H. V. Carey, P. L. Hinton, H. C. Lo and D. M. Ney
Department of Nutritional Sciences, University of Wisconsin, Madison 53706, USA.

Growth hormone (GH) action is primarily mediated by insulin -like growth factor I (IGF-I), although both growth factors show tissue-selective effects. We investigated the effects of GH, IGF-I, and GH plus IGF-I on jejunal growth and function in rats maintained with total parenteral nutrition (TPN) and given recombinant human GH (rhGH) (400 micrograms/day sc, twice daily) and/or rhIGF-I (800 micrograms/day in TPN solution) for 5 days. Administration of GH or IGF-I alone produced similar increases in serum IGF-I levels and body weight; GH plus IGF-I further increased these parameters. TPN reduced mucosal mass, protein and DNA content, villus height, crypt depth, and enterocyte migration rate. IGF-I or GH plus IGF-I produced equivalent increases in all intestinal growth parameters; GH alone had no effect. GH, IGF-I, or GH plus IGF-I reduced TPN-induced increases in sucrase-specific activity. IGF-I, but not GH, attenuated TPN-induced increases in tissue conductance and carbachol-stimulated ion secretion. In contrast to IGF-I, GH does not stimulate intestinal growth during TPN and has less effect on normalizing TPN-induced changes in epithelial function.

Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2
Daniel J. Drucker1, Lorraine Deforest1, and Patricia L. Brubaker1,2

Departments of 1 Medicine and 2 Physiology, Banting and Best Diabetes Centre, Toronto Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4

The control of intestinal epithelial growth is regulated by interactions of growth factors in various cellular compartments of the small and large bowel. Little information is available on the intestinal growth response to combinations of growth factors. We studied the intestinotrophic properties of a dipeptidyl peptidase IV resistant glucagon-like peptide 2 (GLP-2) analog, human [Gly2]GLP-2 (h[Gly2]GLP-2), as well as of epidermal growth factor (EGF), long [Arg3]insulin-like growth factor I (LR3IGF-I), [Gly1]IGF-II, and human growth hormone (hGH), administered by subcutaneous injection alone or in combination in mice. At the doses tested, h[Gly2]GLP-2 was the most potent agent for increasing small and large bowel mass. Mice treated with h[Gly2]GLP-2 and either GH or IGF-I exhibited greater increases in histological parameters of small intestinal growth than did mice treated with h[Gly2]GLP-2 alone. Administration of all five growth factors together induced significant increases in crypt plus villus height and in small and large bowel length and weight. The results of these experiments define regional differences in both the cellular targets and relative activities of intestinotrophic molecules and raise the possibility that selective growth factor combinations may be useful for enhancement of intestinal adaptation in vivo.

protein; bowel; gut; adaptation; mouse



OBJECTIVE: To study the effects and the underlying mechanism of recombinant human growth hormone (rhGH) and glutamine (Gln) on the adaptation of the remnant small intestine in parenterally nourished, short bowel syndrome (SBS) rats.

METHOD: Four parenteral nutrition (PN) treatment groups of SBS rats were randomly arranged in a 2 × 2 factorial design as follows: (i) STD (standard PN) group (–rhGH, –Gln); (ii) Gln group (–rhGH, +Gln); (iii) rhGH group (+rhGH, –Gln); and (iv) rhGH + Gln group (+rhGH, +Gln). Morphological changes of the intestinal mucosa were investigated and the expression of proliferating cell nuclear antigen (PCNA) and the occurrence of apoptosis were observed by immunohistochemical staining and terminal deoxynucleotidyl transfer-mediated dUTP-biotin nick end-labeling (TUNEL) methods. The level of intestinal insulin-like growth factor-1 (IGF-1) mRNA was determined by northern blotting.

RESULTS: The mucosal thickness, villous height, crypt depth and villous surface area of the remnant small intestine in the rhGH + Gln group were increased significantly as compared with the other three experimental groups, and there were synergistic effects between rhGH and Gln (P < 0.01). The expression of PCNA was higher in the rhGH + Gln group than in the rhGH, Gln and STD groups (24.95 ± 3.93 vs 19.28 ± 3.25, 17.27 ± 3.38, and 8.37 ± 2.23 positive cells per crypt of Lieberkuhn, respectively; P < 0.01) but the rate of apoptosis was lower in the rhGH + Gln group than in the rhGH, Gln and STD groups (5.68 ± 2.07 vs 8.06 ± 2.33, 10.00 ± 2.24 and 22.32 ± 3.84 positive cells per 100 cells, respectively; P < 0.01). The intestinal IGF-1 mRNA was also expressed at a higher level in the rhGH + Gln group than in the rhGH, Gln and STD groups (0.73 ± 0.05 vs 0.62 ± 0.04 vs 0.51 ± 0.04 and 0.41 ± 0.22, respectively; P < 0.05).

CONCLUSION: The synergistic combination of rhGH and Gln can significantly improve the adaptation of the remnant small intestine in parenterally fed SBS rats. An increase in cell proliferation and a decrease in cell apoptosis are both responsible for the intestinal adaptation. An increase in local IGF-1 plays an important role in this process.

Just a few studies I figured I'd publish showing experimentation in intestinal growth through growth factors and/or glutamine.... Moral of the story free floating IGF-1 not bound to muscle cells become bound to intestinal cells and cause growth... FACT.... damn I'm board

P.S. like everything else I post on this site noone probably gives a shit lol...

[takincareofbusiness]

Good stuff! So where/how can this information be applied?

[spywizard]

i care..

and bored is the correct spelling.. not board..

your feelings aren't hurt are they??

thanks for sharing.. just to show i read the whole thing.

[956Vette]

through growth factors and/or glutamine....

Have you researched the glutamine aspect very much?

[soulstealer]

Have you researched the glutamine aspect very much?

I have not..... but the only reference I found for its use was specifically for short bowl syndrome... here is a notation I found relating to its effect in the bowel....

Since the pioneering work of Windmueller and Spaeth, the importance of glutamine to the support of intestinal mucosal metabolic function has become generally accepted. Nevertheless, the mechanisms underlying this role still remain obscure. This paper explores a number of questions: 1) Is glutamine essential for intestinal function? 2) To what extent does this relate to its intermediary metabolism? 3) What is the importance of glutamine as a biosynthetic precursor? 4) Is glutamine supplementation of the nutrient mixture presented to patients of any metabolic or clinical benefit? As a result of this exploratory exercise, the following general conclusions were reached: 1) Much suggestive biochemical and physiologic evidence exists that implies that glutamine, especially systemic glutamine, supports the function of the intestinal mucosal system. 2) Despite the extensive metabolism of this amino acid by the intestinal tissues, most evidence suggests that if glutamine does play a physiologic role in the bowel, it is not compellingly related to its intermediary metabolism. 3) There is, on the other hand, evidence that the mucosal cells not only utilize extracellular glutamine but synthesize the amino acid. Given that inhibition of glutamine synthesis inhibits both proliferation and differentiation of mucosal cell cultures, this suggests some more subtle regulatory role. This notion is supported by the demonstration that glutamine will activate a number of genes associated with cell cycle progression in the mucosa. 4) Despite the accumulated evidence, the mechanisms underlying glutamine’s function and the question whether glutamine supplementation uniformly benefits mucosal health remain equivocal at best.

It is important to note that there is specific mention of HGH and its positive effects of nutrient absorption in the intestine I believe in these studies specifically for SBS the HGH's primary role was two pronged increased glutamine uptake/intestinal growth through elevated IGF1 levels...

[soulstealer]

i care..

and bored is the correct spelling.. not board..

your feelings aren't hurt are they??

thanks for sharing.. just to show i read the whole thing.

good stuff glad someones reading

[soulstealer]

Good stuff! So where/how can this information be applied?

Well its become a pretty common practice in higher level bodybuilding to combine HGH and IGF1 for enhanced insulin sensitivity and bonding of IGF-1 to receptor sights immediately PWO HGH having similar properties in elevation of IGF-1 levels and reduction in bodyfat.... there happens to be a terrible side effect which has gotten the name "palumboism" big gut and weird looking elbows... I believe whats to be learned here is large dosages of IGF-1 and HGH will cause nasty, nasty sides and pretty quick..... HGH being the obviously safer choice....

[956Vette]

I have not.....

I remember a lot of my studies back in the day led me to believe oral glut supplementation was garbage/mostly ineffective. Thanks for posting those