Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats.
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.
Fischer
K D
KD
Department of Physiology, The Toronto Hospital, University of Toronto, Ontario, Canada.
Dhanvantari
S
S
Drucker
D J
DJ
Brubaker
P L
PL
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005768:Gastrointestinal Hormones / Q000096:biosynthesis*; D053771:Glicentin; D005934:Glucagon / Q000096:biosynthesis / Q000378:metabolism; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007421:Intestine, Small / Q000033:anatomy & histology / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D009928:Organ Specificity; D053772:Oxyntomodulin; D010446:Peptide Fragments / Q000096:biosynthesis; D010455:Peptides / Q000378:metabolism*; D052336:Proglucagon; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D007328:Insulin; D053772:Oxyntomodulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D004763:Glucagon-Like Peptides; D053771:Glicentin; D005934:Glucagon