Dexamethasone and GLP-2 administered to rat dams during pregnancy and lactation have late effects on intestinal sugar transport in their postweaning offspring.
Intestinal function in young animals is influenced by maternal factors, such as alterations in the maternal diet. Glucagon-like peptide 2 (GLP-2) enhances intestinal growth and absorption in mature animals. Glucocorticosteroids induce intestinal maturation in neonates and increase sugar uptake in adult animals. It is not known if maternally administered GLP-2 or glucocorticosteroids have persistent effects on intestinal transport in the offspring. This study was undertaken to determine (1) the influence of maternal GLP-2, dexamethasone (DEX) and GLP-2+DEX on intestinal sugar uptake in postweaning offspring and (2) if alterations in uptake are due to variations in intestinal morphology, sugar transporter abundance or the abundance of selected signals. Nursing rat dams were treated during pregnancy and lactation with GLP-2 (0.1 mug/g per day sc), DEX (0.128 microg/g per day sc), GLP-2+DEX or placebo. The offspring were sacrificed 4 weeks after weaning, and glucose and fructose uptake was determined using an in vitro intestinal ring uptake technique. sodium-dependent glucose transporter, glucose transporter (GLUT) 5, GLUT2, sodium potassium adenosine triphosphatase and selected signals were assessed by immunohistochemistry. The treatments did not affect body weights or intestinal morphology. GLP-2 and GLP-2+DEX increased jejunal fructose uptake, and GLP-2+DEX increased the jejunal and ileal maximal transport rate for glucose uptake. Protein kinase B and mammalian target of rapamycin abundance were also increased, while transporter abundance was unchanged. We speculate that these alterations in sugar uptake may be due to changes in the intrinsic activity of the transporters mediated by the phosphatidylinositol-3-kinase pathway. These alterations in uptake may have nutritional implications for the offspring of mothers who may be treated with GLP-2 or glucocorticosteroids.
Drozdowski
Laurie A
LA
Nutrition and Metabolism Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2N8. lad2@ualberta.ca <lad2@ualberta.ca>
Iordache
Claudiu
C
Clandinin
M Tom
MT
Todd
Zoe S C
ZS
Gonnet
Maud
M
Wild
Gary
G
Uwiera
Richard R E
RR
Thomson
Alan B R
AB
D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005632:Fructose / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000032:analysis; D051296:Glucose Transporter Type 5 / Q000032:analysis; D006601:Hexoses / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000033:anatomy & histology / Q000737:chemistry; D007774:Lactation; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011494:Protein Kinases / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000032:analysis; D058570:TOR Serine-Threonine Kinases; D014886:Weaning
D053767:Glucagon-Like Peptide 2; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D006601:Hexoses; C495683:Slc2a2 protein, rat; C495727:Slc2a5 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D005632:Fructose; D003907:Dexamethasone; D011494:Protein Kinases; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose