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Am J Physiol Endocrinol Metab 273: E815-E820, 1997;
0193-1849/97 $5.00
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Vol. 273, Issue 4, E815-E820, October 1997

Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats

Kirk D. Fischer1, Savita Dhanvantari1, Daniel J. Drucker2,3, and Patricia L. Brubaker1,2

Departments of 1 Physiology and 2 Medicine and the 3 Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Glucagon-like peptide 2 (GLP-2) has recently been identified as a novel intestinal growth factor. Because 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 and treated with or without insulin for 3 wk. Ileal concentrations of the intestinal proglucagon-derived peptides, i.e., glicentin + oxyntomodulin, and GLPs 1 and 2, were increased by 57 ± 20% above those of controls in untreated STZ diabetes (P < 0.05-0.001). Similar increases in plasma concentrations of glicentin + oxyntomodulin (77 ± 15% above controls, P < 0.01) and GLP-2 (91 ± 32% above controls, P < 0.05) were seen in untreated STZ diabetes. Both wet and dry small intestinal weight increased by 74 ± 20% above controls (P < 0.01) in STZ diabetes, and macromolecular analysis indicated parallel increases in both protein (P < 0.001) and lipid (P < 0.05) content. Villus height (P < 0.001) and crypt depth (P < 0.01) were also increased in untreated diabetic rat intestine. Insulin therapy prevented the changes in plasma GLP-2 and intestinal mass seen in untreated STZ diabetes. 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.

small intestine; adaptation


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