Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats.
Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2 in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies, (3) diabetic rats treated with polyclonal GLP-2 antibodies and (4) non-diabetic control rats treated with saline. All animals were treated with once daily intraperitoneal injections for 13 days and killed on day 14. Diabetic rats treated with saline or non-specific antibodies had a significantly (P<0.01) increased area of mucosa (13.00+/-0.64 and 13.37+/-0.60 mm(2), respectively) in the proximal part of the small intestine compared with non-diabetic controls (7.97+/-0.70 mm(2)). In contrast, diabetic rats treated with GLP-2 antibodies had a significantly (P<0.01) smaller increase in area of mucosa in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological growth factor function of GLP-2.
Hartmann
Bolette
B
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
Thulesen
Jesper
J
Hare
Kristine Juul
KJ
Kissow
Hannelouise
H
Orskov
Cathrine
C
Poulsen
Steen Seier
SS
Holst
Jens Juul
JJ
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D003920:Diabetes Mellitus / Q000378:metabolism*; D004435:Eating; D005260:Female; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000033:anatomy & histology / Q000254:growth & development*; D009500:Neutralization Tests; D009929:Organ Size; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides