Abstract
Growth hormone (GH) and glutamine (Gln) stimulate the growth of the intestinal mucosa. GH activates the proliferation of intestinal stem cells (ISCs), enhances the formation of crypt organoids, increases ISC stemness markers in the intestinal organoids, and drives the differentiation of ISCs into Paneth cells and enterocytes. Gln enhances the proliferation of ISCs and increases crypt organoid formation; however, it mainly acts on the post-proliferation activity of ISCs to maintain the stability of crypt organoids and the intestinal mucosa, as well as to stimulate the differentiation of ISCs into goblet cells and possibly Paneth cells and enteroendocrine cells. Since GH and Gln have differential effects on ISCs. Their use in combination may have synergistic effects on ISCs. In this review, we summarize the evidence of the actions of GH and/or Gln on crypt cells and ISCs in the literature. Overall, most studies demonstrated that GH and Gln in combination exerted synergistic effects to activate the proliferation of crypt cells and ISCs and enhance crypt organoid formation and mucosal growth. This treatment influenced the proliferation of ISCs to a similar degree as GH treatment alone and the differentiation of ISCs to a similar degree as Gln treatment alone.
Highlights
Most studies demonstrated that Growth hormone (GH) and Gln in combination exerted synergistic effects to activate the proliferation of crypt cells and intestinal stem cells (ISCs) and enhance crypt organoid formation and mucosal growth
A meta-analysis including 13 trials and involving 258 patients with short bowel syndrome (SBS) demonstrated that GH+Gln with a modified high-carbohydrate-low-fat diet had a positive effect on body weight, stool output, and lean body mass as well as the absorption of carbohydrates, nitrogen, and D-xylose, and weaning off total parenteral nutrition (TPN) [98]. These results indicate that the effects of combined GH and Gln on various intestinal disorders are inconsistent; most of the results demonstrate that GH+Gln exerts a synergistic effect on the intestinal absorption of nutrients, intestinal adaptation, intestinal cell proliferation, general nutritional status, and reduced dependence of parenteral nutrition in SBS patients
GH treatment requires an adequate supply of nutrients, such as a high protein diet, in order to stimulate the intestinal mucosa in aged animals [37]
Summary
The intestine comprises mucosa, submucosa, muscle layers, and serosa, as well as intestinal stem cells (ISCs) located at or near the crypt base of the mucosa (Figure 1) [1,2,3]. The intestinal epithelial cells are renewed every four to five days, and when proliferation is activated, ISCs undergo terminal differentiation as they migrate to the luminal surface [1,2,7,8,9]. The structural and the functional changes in the remaining intestine post operation, which peaks within 1–2 weeks of surgery, the development of which is limited to four usually begin on the second post-operative day, after which the intestinal wall width and crypt weeks after intestinal resection [21,35,36] These changes are generally not enough to support depth significantly increase as early as the fifth day post operation, which peaks within 1–2 weeks of the capacity of the intestine to absorb nutrients in SBS [37]. We discuss the influence of combined GH and Gln on the proliferation and the differentiation of the ISCs and propose possible clinical applications of this combination in intestinal diseases
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