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Published on: November 15, 2019
Oral polyamine administration modifies the ontogeny of hexose transporter gene expression in the postnatal rat
G E Wild1, L E Searles, K G Koski
1Division of Gastroenterology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
Insights
Oral spermidine administration in young rats precociously enhances small intestinal maturation. This polyamine treatment upregulated ornithine decarboxylase (ODC), boosting sugar transporter expression and promoting faster development of the gut lining.
Area of Science:
- Gastroenterology
- Developmental Biology
- Molecular Nutrition
Background:
- Gastrointestinal mucosal polyamines are crucial for enterocyte proliferation and differentiation during small intestinal maturation in rats.
- Ornithine decarboxylase (ODC) expression peaks before key brush-border membrane (BBM) enzymes and sugar transporters, including sucrase-isomaltase (SI), sodium-dependent glucose transporter 1 (SGLT1), and glucose transporter 2 (GLUT2).
Purpose of the Study:
- To investigate the hypothesis that oral spermidine administration upregulates ODC expression in postnatal rats.
- To determine if spermidine enhances the expression of SI, SGLT1, GLUT2, and Na(+)-K(+)-ATPase in the small intestine.
- To assess the impact of spermidine on the maturation of glucose transporters and related enzymes.
Main Methods:
- Postnatal rats (days 7-9) received daily oral administration of 6 mumol spermidine.
- Northern and Western blot analyses were used to quantify specific mRNAs and proteins (SI, SGLT1, GLUT2, Na(+)-K(+)-ATPase alpha(1) and beta(1) subunits, ODC).
- Animals were analyzed on postnatal day 10 (Sp10) or after a 3-day washout on day 13 (Sp13).
Main Results:
- Sp10 rats exhibited a precocious increase in mRNA abundance for SI, SGLT1, and GLUT2, along with elevated Na(+)-K(+)-ATPase activity and gene expression.
- ODC activity, protein, and mRNA levels were significantly increased in spermidine-treated Sp10 rats compared to controls.
- These enhanced expressions were transient, as they were not sustained in Sp13 rats following the washout period.
Conclusions:
- Three days of oral polyamine administration, specifically spermidine, induces precocious maturation of glucose transporters in the postnatal rat small intestine.
- The observed effects may be mediated by spermidine-induced alterations in ornithine decarboxylase (ODC) expression.
- Polyamines represent a potential therapeutic target for modulating intestinal development and nutrient absorption.
Abstract:
Gastrointestinal mucosal polyamines influence enterocyte proliferation and differentiation during small intestinal maturation in the rat. Studies in postnatal rats have shown that ornithine decarboxylase (ODC) protein and mRNA peak before the maximal expression of brush-border membrane (BBM) sucrase-isomaltase (SI) and the sugar transporters sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2). This study was undertaken to test the hypothesis that the oral administration of spermidine in postnatal rats upregulates the expression of ODC, thereby enhancing the expression of SI and SGLT1 in the brush-border membrane as well as basolateral membrane-facilitative GLUT2 and Na(+)-K(+)-ATPase. Northern and Western blot analyses were performed with antibodies and cDNA probes specific for SI, SGLT1, GLUT2, alpha(1)- and beta(1)-subunits of Na(+)-K(+)-ATPase, and ODC. Postnatal rats fed 6 mumol spermidine daily for 3 days from days 7 to 9 were killed either on postnatal day 10 (Sp10) or day 13 following a 3-day washout period (Sp13). Sp10 rats showed a precocious increase in the abundance of mRNAs for SI, SGLT1, and GLUT2 and Na(+)-K(+)-ATPase activity and alpha(1)- and beta(1)-isoform gene expression compared with controls. ODC activity and protein and mRNA abundance were also increased in Sp10 animals. The increased expression of these genes was not sustained in Sp13 rats, suggesting that these effects were transient. Thus, 3 days of oral polyamine administration induces the precocious maturation of glucose transporters in the postnatal rat small intestine, which may be mediated by alterations in ODC expression.

