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.

A combination of dexamethasone and glucagon-like peptide-2 increase intestinal morphology and glucose uptake in suckling rats.

OBJECTIVES: Glucagon-like peptide (GLP)-2 enhances nutrient uptake in adult animals. Glucocorticosteroids accelerate intestinal ontogeny and increase nutrient uptake in adult animals. We hypothesized that administering GLP-2 and dexamethasone (DEX) to suckling rats will enhance sugar uptake and that this effect persists into the postweaning period. METHODS: Suckling rats were treated for 10 days with GLP-2 (0.1 microg/g/d, twice daily), DEX (0.128 microg/g/d, once daily), GLP-2 + Dex (same doses as above), or placebo. The rate of intestinal uptake of glucose and fructose in sucklings (19-21 days old) and weanlings (49 days old) was assessed using an in vitro ring technique. RESULTS: DEX reduced body weight in weanlings, whereas GLP-2 + DEX prevented this effect. In sucklings, GLP-2 + DEX increased ileal villous height and jejunal and ileal villous width and crypt depth. In sucklings, GLP-2 + DEX increased the maximal transport rate (Vmax) for jejunal glucose uptake, whereas DEX reduced the ileal Vmax. In weanlings, GLP-2 + DEX increased jejunal villous height, whereas ileal villous width and crypt depth were reduced. DEX increased the ileal Vmax and apparent affinity constant for glucose in weanlings. CONCLUSIONS: The combination of these hormones may be useful in stimulating glucose uptake in the developing intestine, and giving DEX to sucklings may enhance glucose uptake in later life.

Lipid malabsorption persists after weaning in rats whose dams were given GLP-2 and dexamethasone.

Glucagon-like peptide-2 (GLP-2) enhances intestinal growth and absorption in mature animals, and glucocorticosteroids (GC) increase the sugar and lipid uptake in adult animals. However, the role of GC and GLP-2 in the ontogeny of lipid absorption is unknown. We hypothesized that GLP-2 and the GC dexamethasone (DEX), when administrated to rat dams during pregnancy and lactation, would enhance lipid uptake in the offspring. Rat dams were treated in the last 10 d of pregnancy and during lactation with GLP-2 [0.1 microg/g/d subcutaneous (sc)], DEX (0.128 microg/g/d sc), GLP-2 + DEX, or a placebo. Sucklings were sacrificed at 19-21 d of age, and weanlings were sacrificed 4 wk later. Lipid uptake was assessed using an in vitro ring uptake method. Although DEX and GLP-2 + DEX increased the jejunal mass, the jejunal lipid uptake was unchanged. In contrast, GLP-2, DEX, and GLP-2 + DEX reduced the ileal lipid uptake in suckling and weanling rats. This reduction was not due to alterations in intestinal morphology or to changes in fatty acid-binding protein abundance, but it was partially explained by an increase in the effective resistance of the intestinal unstirred water layer. In sucklings, DEX dramatically reduced the jejunal lipid uptake to levels similar to those seen in weanlings, such that the normal ontogenic decline in lipid uptake was not observed. Giving dams GLP-2 or DEX during pregnancy and lactation reduced lipid uptake in the offspring, and this persisted for at least 1 mon. The impact this may have on the nutritional well-being of the animal in later life is unknown.

Treatment of suckling rats with GLP-2 plus dexamethasone increases the ileal uptake of fatty acids in later life.

Glucocorticosteroids such as dexamethasone (Dex) increase sugar and lipid uptake in adult animals and accelerate the development of the immature intestine. The effect of Dex on the ontogeny of lipid absorption is unknown. In adult rats, glucagon-like peptide-2 (GLP-2) has a trophic effect on the intestine and enhances nutrient absorption. This study was undertaken to determine the effect of GLP-2 and Dex on the intestine uptake of lipids in suckling rats and to determine whether any such effect persists into the postweanling period. Sixty-four suckling rats were randomized into four groups. They were treated from days 11 to 21 with GLP-2 (0.1 microg.g(-1).day(-1) sc), Dex (0.128 microg.g(-1).day(-1) sc), GLP-2 plus Dex (GLP-2 0.1 microg.g(-1).day(-1) sc + Dex 0.128 microg.g(-1).day(-1) sc), or placebo. One-half the pups were killed at days 19-21 ("sucklings"), and one-half were killed 4 wk later ("weanlings"). The rate of intestinal uptake of six fatty acids (12:0, lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3, linolenic) and cholesterol was assessed using an in vitro ring technique. GLP-2 had no effect on lipid uptake. Dex increased the uptake of 18:3 in sucklings, and the ileal uptake of 18:0 was increased in weanlings. The combination of GLP-2 plus Dex had no effect in sucklings and increased the ileal uptake of 12:0, 18:0, 18:1, 18:2, and 18:3 in weanlings. The enhanced uptake of fatty acids with GLP-2 plus Dex was not explained by alterations in the animals' body or intestinal weights, intestinal morphology, or intestinal- or liver-fatty acid binding proteins. Unlike adults, GLP-2 does not enhance lipid uptake in sucklings. Dex has a modest enhancing effect on selected fatty acid uptake both in sucklings as well as weanlings. GLP-2 plus Dex has an enhancing effect on the ileal uptake of fatty acids in weanlings 4 wk after their previous injection with GLP-2 plus Dex. It remains to be established what is the nutritional importance of this late effect of prior exposure to Dex or GLP-2 plus Dex on the intestinal uptake of lipids.

Dexamethasone plus glucagon-like peptide 2 given to lactating rat dams has a late effect on intestinal lipid uptake in the weanling offspring.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) has a trophic effect on the intestine and enhances intestinal absorption in adult animals, but its effect in young rats is unknown. Glucocorticosteroids accelerate the ontogeny of the intestine, and in adult animals they increase the uptake of sugars and lipids. We hypothesized that GLP-2 and dexamethasone (DEX), when administrated to lactating rat dams, will enhance lipid uptake in the suckling and weanling offspring. METHODS: Eight nursing rats were treated during lactation, 19 to 21 days, with GLP-2 (0.1 microg/g/d subcutaneously [s.c.]), DEX (0.128 microg/g/d s.c.), GLP-2 + DEX (GLP-2 0.1 microg/g/d s.c. plus DEX 0.128 microg/g/d s.c.), or placebo. Half of the offspring ("sucklings") were killed at 19 to 21 days of age, and half were killed 4 weeks later ("weanlings"). The rate of intestinal uptake of fatty acids (12:0, lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3, linolenic) and cholesterol were assessed using an in vitro ring technique. RESULTS: GLP-2 and DEX resulted in loss of body weight in sucklings, which was prevented by giving the combination GLP-2 + DEX. The jejunal atrophy in sucklings given DEX was prevented by giving GLP-2 + DEX, but GLP-2 + DEX did not prevent the decline in jejunal and ileal villous height and crypt depth observed in weanlings given DEX. GLP-2 had little effect on lipid uptake in sucklings, whereas DEX or GLP-2 + DEX increased the uptake of lipids. In contrast, in weanlings there was malabsorption of several lipids with GLP-2 or GLP-2 + DEX, but not with DEX. Lipid uptake was lower in weanlings than in sucklings, and this age-associated decline was not altered by GLP-2 or DEX. CONCLUSIONS: The loss of body weight and the jejunal atrophy induced by DEX in sucklings is prevented by adding GLP-2. Giving DEX or GLP-2 + DEX to lactating mothers enhances lipid uptake in their suckling offspring. In marked contrast, a month after lactating dams were given GLP-2 or GLP-2 + DEX, there was reduced lipid absorption in the postweaning animals. Thus, giving GLP-2 + DEX during lactation may be useful to enhance lipid uptake in the suckling offspring, without adverse effects on body weight or intestinal characteristics. However, the late effects of this treatment on lipid absorption were of concern, and could be potentially deleterious to the nutritional well-being of the animal.