Location: Children's Nutrition Research CenterTitle: Apical Na(+)-D-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig Author
|Burrin, Douglas - Doug|
Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2010
Publication Date: 10/28/2010
Citation: Yang, C., Albin, D.M., Wang, Z., Stoll, B., Lackeyram, D., Swanson, K.C., Yin, Y., Tappenden, K.A., Mine, Y., Yada, R.Y., Burrin, D.G., Fan, M.Z. 2011. Apical Na[+]-D-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig. American Journal of Physiology - Gastrointestinal and Liver Physiology. 300(1):G60-G70. Interpretive Summary: The absorption of dietary sugars is a vital function of the intestine in young infants. The main sugar present in milk consumed by infants is lactose, which is made up from two simple sugar molecules, glucose and galactose. Both of these simple sugars are absorbed from the gut into the blood by a protein, called sodium glucose cotransporter 1 (SGLT1), made by cells along the intestine. The goal of this study was to determine the cell mechanism that regulates the production of SGLT1 in intestinal cells present along the villus, which is a finger-like projection of the gut that increases the surface area for absorption. We found that the SGLT1 protein was found in all cells along the gut villus, including newly produced crypt cells and mature villus cells. However, the amount of the genetic message or mRNA that produces SGLT1 was lower in crypt cells than mature villus cells. We also found that the activity of cell proteins that increase the efficiency of protein production were higher in crypt vs. mature villus cells. The results suggest that the changes in the production of cell signals leads to higher expression of sugar transport proteins along the entire surface of the neonatal intestine.
Technical Abstract: Gut apical Na(+)-glucose cotransporter 1 (SGLT1) activity is high at the birth and during suckling, thus contributing substantially to neonatal glucose homeostasis. We hypothesize that neonates possess high SGLT1 maximal activity by expressing apical SGLT1 protein along the intestinal crypt-villus axis via unique control mechanisms. Kinetics of SGLT1 activity in apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from neonatal piglets by the distended intestinal sac method, were measured. High levels of maximal SGLT1 uptake activity were shown to exist along the jejunal crypt-villus axis in the piglets. Real-time RT-PCR analyses showed that SGLT1 mRNA abundance was lower ("P" < 0.05) by 30–35 percent in crypt cells than in villus cells. There were no significant differences in SGLT1 protein abundances on the jejunal apical membrane among upper villus, middle villus, and crypt cells, consistent with the immunohistochemical staining pattern. Higher abundances ("P" < 0.05) of total eukaryotic initiation factor 4E (eIF4E) protein and eIE4E binding protein 1 gamma-isoform in contrast to a lower ("P" < 0.05) abundance of phosphorylated (Pi) eukaryotic elongation factor 2 (eEF2) protein and the eEF2-Pi to total eEF2 abundance ratio suggest higher global protein translational efficiency in the crypt cells than in the upper villus cells. In conclusion, neonates have high intestinal apical SGLT1 uptake activity by abundantly expressing SGLT1 protein in the epithelia and on the apical membrane along the entire crypt-villus axis in association with enhanced protein translational control mechanisms in the crypt cells.