Intestinal growth in models of glucagon-like peptide-2 overexpression

grantor: University of TorontoExogenous glucagon-like peptide-2 (GLP-2) has been shown to be a potent and specific stimulator of small intestinal mucosal proliferation in vivo. However, to date no studies have looked at the role of endogenous GLP-2 in the control of bowel growth. As experimental diabetes is associated with bowel growth, we examined the relationship between GLP-2 and intestinal growth in rats made diabetic by streptozotocin (STZ) injection, treated with or without insulin for three weeks. Compared to non-diabetic control animals, untreated diabetic rats showed increases in ileal and plasma GLP-2 $(p < 0.05)$, wet and dry small intestinal weight $(p < 0.01)$, intestinal protein $(p < 0.001)$ and lipid $(p < 0.05)$ content, villus height $(p < 0.001)$, and crypt depth $(p < 0.01).$ Thus, STZ-diabetes is associated with both increased production of GLP-2 and enhanced bowel weight, thereby suggesting a role for GLP-2 in diabetes-associated bowel growth. To develop a specific GLP-2 overexpression system, Baby Hamster Kidney cells were transfected with a cDNA construct consisting of the coding region of human proglucagon signal peptide fused to that for human GLP-2. These cells successfully transcribed the construct but failed to synthesize or secrete GLP-2 peptide. In conclusion, this study supports a role for GLP-2 as an endogenous intestinal growth factor and provides a basis for future work on the development of a GLP-2 overexpression system.M.Sc