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Laurie A Drozdowski

Publications and source records attributed to Laurie A Drozdowski.

8 recordsLinked to original sources

Intestinal sugar transport.

Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides (glucose, fructose and galactose) to disaccharides (lactose, sucrose) to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane (BBM) of enterocytes. For example, lactase-phloridzin hydrolase and sucrase-isomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.

Animals↗

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.

Animals↗

Dietary gangliosides enhance in vitro lipid uptake in weanling rats.

BACKGROUND: The intestine adapts morphologically or functionally in response to environmental stimuli. Dietary lipids modify brush border membrane (BBM) permeability and nutrient transporter activities. Gangliosides (GANG) are glycolipids in human milk that are present only in low amounts in infant formula. Exogenous GANG are incorporated into cell membranes and increase their permeability. The objective of this study was to determine whether feeding a GANG-enriched diet alters in vitro intestinal lipid absorption. METHODS: Weanling rats were fed either (1) GANG-enriched diet; (2) diet enriched with polyunsaturated long-chain fatty acids; or (3) isocaloric control diet for 2 weeks, after which in vitro intestinal lipid uptake was measured. RESULTS: Feeding GANG did not alter weight gain or intestinal morphology. Enhanced uptake of stearic acid (18:0) in the ileum and stearic and linoleic acid (18:2) in the jejunum was not associated with a change in the abundance of the ileal lipid binding protein (ILBP), the intestinal fatty acid binding protein (I-FABP), or the liver fatty acid binding protein (L-FABP). CONCLUSION: We speculate that the enhanced uptake of long-chain fatty acids in weanling rats fed GANG may be caused by a modification in physical properties of the BBM.

Adaptation, Physiological↗

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.

Animals↗

An isocaloric PUFA diet enhances lipid uptake and weight gain in aging rats.

Aging is associated with a change in the morphology and absorptive capacity of the small intestine. In young rats, feeding a semisynthetic diet containing saturated FA (SFA) increases nutrient uptake, as compared with an isocaloric diet containing polyunsaturated FA (PUFA). We tested the hypotheses that (i) aging is associated with a decline in lipid absorption in the Fischer 344 rat; (ii) this decline can be corrected by manipulating the fat composition of the diet; and (iii) the age- and diet-associated variations in lipid uptake are associated with changes in the ileal lipid-binding protein (ILBP) or the intestinal or liver FA-binding proteins (I- or L-FABP, respectively) in the cytosol of the enterocyte. In rats fed SFA or PUFA, aging was associated with a decline in the in vitro uptake of stearic acid (18:0) when expressed on the basis of intestinal or mucosal weight. In contrast, age had no effect on lipid uptake when expressed on the basis of serosal surface area, whereas lipid uptake increased with age when expressed on the basis of mucosal surface area. The age-associated variations in lipid uptake were not associated with changes in protein abundance and/or expression of ILBP, I-FABP, or L-FABP. In 24-mon-old rats, when uptake of lipids was expressed on the basis of mucosal surface area, feeding PUFA enhanced lipid uptake and body weight gain as compared with rats fed SFA. Future studies must determine whether the enhanced lipid uptake and body weight gain observed in older animals fed PUFA have any therapeutic benefit.

Aged↗

The age-related decline in intestinal lipid uptake is associated with a reduced abundance of fatty acid-binding protein.

Aging is associated with changes in the absorptive capacity of the small intestine. We tested the hypotheses that (i) aging is associated with a decline in lipid absorption, and that (ii) this decreased lipid absorption is due to a decline in the abundance of mRNA and/or the enterocyte cytosolic intestinal FA-binding protein (I-FABP), the liver FA-binding protein (L-FABP), and the ileal lipid-binding protein (ILBP). In vitro uptake studies were performed on Fischer 344 rats at ages 1, 9, and 24 mon. Northern blotting (L-FABP, ILBP) and immunohistochemistry (I-FABP, ILBP) were performed. Aging was associated with decreased animal weights, but the surface area of the intestine was not significantly altered with age. The rates of ileal uptake of 16:0, 18:0, 18:1, and 18:2 were reduced by greater than 50% with aging when expressed on the basis of mucosal weight. This decline was not associated with reduced expression of mRNA for L-FABP or ILBP but was associated with a 50% decrease in the abundance of I-FABP and a 40% decrease in the abundance of ILBP. Thus, the decrease with aging in the ileal uptake of some FA when rates were expressed on the basis of mucosal weight was associated with a reduced abundance of I-FABP and ILBP.

Aging↗

Age-associated changes in intestinal fructose uptake are not explained by alterations in the abundance of GLUT5 or GLUT2.

A reduction in nutrient absorption may contribute to malnourishment in the elderly. The objectives of this study were to determine the effects of aging on the absorption of fructose in rats, as well as the mechanisms of these adaptive changes. Male Fischer 344 rats aged 1, 9, and 24 months were fed standard Purina chow for 2 weeks (PMI #5001, PMI Nutritionals, Brentwood, MO). The uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal sheet method. Intestinal samples were taken for RNA isolation and for brush border membrane (BBM) and basolateral membrane (BLM) preparation. Northern blotting, Western blotting, and immunohistochemistry were used to determine the effects of age and diet on GLUT5 and GLUT2. When expressed on the basis of intestinal or mucosal weights, aging was associated with a decline in jejunal and ileal fructose uptake, whereas jejunal fructose uptake was increased when expressed on the basis of serosal or mucosal surface area. The alterations in fructose uptake were not paralleled by changes in GLUT5 or GLUT2 abundance. These results indicate that 1) the effect of age on fructose uptake depends on the method used to express results, and 2) the age-associated changes in uptake are not explained by alterations in GLUT5 and GLUT2.

Aging↗

Short-chain fatty acids and total parenteral nutrition affect intestinal gene expression.

BACKGROUND: The supplementation of total parenteral nutrition (TPN) formulas with short-chain fatty acids (SCFAs) increases glucose uptake and the expression of glucose transporters in parenterally fed animals. Several signals may be involved in intestinal adaptation; however, increased messenger RNA (mRNA) levels for proglucagon and several early-response genes, including c-myc and c-fos, are seen in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of SCFAs are well documented, the relative contribution of individual SCFAs is unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on cellular proliferation and gene expression. Accordingly, this study was undertaken to determine the relative role of butyrate in initiating an adaptive response in nonresected rats receiving TPN. METHODS: Animals received standard TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an elemental diet, similar in macronutrient content to the TPN, so that all animals received the same amount of energy daily. RESULTS: SCFAs increased ileal glucose transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs also increased proglucagon mRNA expression compared with the TPN group. No changes in Na+K(+)-adenosine triphosphatase or early-response gene expression were found in this study. CONCLUSIONS: In a rat model of TPN, the use of 9 mmol/L butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60-mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on intestinal gene expression is not butyrate specific.

Animals↗