Expression of ileal glucagon and peptide tyrosine-tyrosine genes. Response to inhibition of polyamine synthesis in the presence of massive small-bowel resection

Abstract

Massive small-bowel resection results in a marked adaptive response in the residual terminal ileum. Increased polyamine synthesis is a necessary component of this response. The ileal L-cell-derived peptides enteroglucagon and peptide tyrosine tyrosine (PYY) have been implicated as humoral mediators of this response. We have previously reported a rapid and sustained increase in glucagon mRNA concentrations after massive small-bowel resection. In this study using an inhibitor of the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase, we have demonstrated that the response of the glucagon and PYY genes to massive small-bowel resection is dependent on polyamine biosynthesis. In addition, we have examined the response of both the ornithine decarboxylase and c-jun genes in this model of intestinal adaptation.

The role of gut hormones in glucose homeostasis

“…Intestinal injury and resection are both associated with elevated circulating levels of PGDPs and increased levels of proglucagon mRNA in the remnant intestine (29,30). PGDP secretion by enteroendocrine L cells is stimulated by neural signals, peptide hormones such as GIP (in rodents but not humans), and direct nutrient contact (31).…”

Gut adaptation and the glucagon-like peptides

“…15 Intestinal resection was consistently associated with increased circulating levels of the PGDPs and upregulation of intestinal proglucagon mRNA transcripts in the intestinal remnant. [16][17][18][19] Injury to the gastrointestinal epithelium is also associated with increased circulating levels of the PGDPs in human subjects. Patients with jejunoileal bypass procedures exhibited elevations in circulating enteroglucagon, hyperplasia in the intestinal remnant, and preservation of the mucosal epithe-lium in the bypassed intestinal segment.…”

Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model

“…Although short bowel syndrome models have been developed by using different animal species, rodent models have been used extensively to assess the process of intestinal adaptation and the mechanisms underlying the response to changes in diet composition. 8,9,[11][12][13][14][15][16] However, there are important anatomical, physiological and biochemical differences between the rodent and human gastrointestinal tract, which makes it difficult to extrapolate findings from the rodent model. 17 There are also important differences in the growth rate and developmental physiology between adult and infant animals.…”