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Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors.
Surgery 2009; 145(3):294-302S

Abstract

BACKGROUND

The intestinal sodium-glucose cotransporter 1 (SGLT1) is responsible for all secondary active transport of dietary glucose, and it presents a potential therapeutic target for obesity and diabetes. SGLT1 expression varies with a profound diurnal rhythm, matching expression to nutrient intake. The mechanisms entraining this rhythm remain unknown. We investigated the role of local nutrient signals in diurnal SGLT1 entrainment.

METHODS

Male Sprague-Dawley rats, which were acclimatized to a 12:12 light:dark cycle, underwent laparotomy with formation of isolated proximal jejunal loops (Thiry-Vella loops). Animals were recovered for 10 days before harvesting at 4 6-h intervals (Zeitgeber times ZT3, ZT9, ZT15, and ZT21, where ZT0 is lights on; n = 6-8). SGLT1 expression was assessed in protein, and mRNA extracts of mucosa were harvested from both isolated loops (LOOP) and remnant jejunum (JEJ).

RESULTS

Isolated loops were healthy but atrophic with minimal changes to villus architecture. A normal anticipatory rhythm was observed in Sglt1 transcription in both LOOP and JEJ, with the peak signal at ZT9 (2.7-fold, P < .001). Normal diurnal rhythms were also observed in the protein signal, with peak expression in both LOOP and JEJ at ZT9 to 15 (2.1-fold, P < .05). However, an additional more mobile polypeptide band was also observed in all LOOP samples but not in JEJ samples (61 kDa vs 69 kDa). Enzymatic deglycosylation suggested this to be deglycosylated SGLT1.

CONCLUSION

The persistence of SGLT1 rhythmicity in isolated loops indicates that diurnal induction is independent of local luminal nutrient delivery, and it suggests a reliance on systemic entrainment pathways. However, local luminal signals may regulate glycosylation and, therefore, the posttranslational handling of SGLT1.

Authors+Show Affiliations

Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19231582

Citation

Stearns, Adam T., et al. "Diurnal Expression of the Rat Intestinal Sodium-glucose Cotransporter 1 (SGLT1) Is Independent of Local Luminal Factors." Surgery, vol. 145, no. 3, 2009, pp. 294-302.
Stearns AT, Balakrishnan A, Rhoads DB, et al. Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors. Surgery. 2009;145(3):294-302.
Stearns, A. T., Balakrishnan, A., Rhoads, D. B., Ashley, S. W., & Tavakkolizadeh, A. (2009). Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors. Surgery, 145(3), pp. 294-302. doi:10.1016/j.surg.2008.11.004.
Stearns AT, et al. Diurnal Expression of the Rat Intestinal Sodium-glucose Cotransporter 1 (SGLT1) Is Independent of Local Luminal Factors. Surgery. 2009;145(3):294-302. PubMed PMID: 19231582.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors. AU - Stearns,Adam T, AU - Balakrishnan,Anita, AU - Rhoads,David B, AU - Ashley,Stanley W, AU - Tavakkolizadeh,Ali, Y1 - 2009/02/01/ PY - 2008/07/11/received PY - 2008/11/13/accepted PY - 2009/2/24/entrez PY - 2009/2/24/pubmed PY - 2009/3/7/medline SP - 294 EP - 302 JF - Surgery JO - Surgery VL - 145 IS - 3 N2 - BACKGROUND: The intestinal sodium-glucose cotransporter 1 (SGLT1) is responsible for all secondary active transport of dietary glucose, and it presents a potential therapeutic target for obesity and diabetes. SGLT1 expression varies with a profound diurnal rhythm, matching expression to nutrient intake. The mechanisms entraining this rhythm remain unknown. We investigated the role of local nutrient signals in diurnal SGLT1 entrainment. METHODS: Male Sprague-Dawley rats, which were acclimatized to a 12:12 light:dark cycle, underwent laparotomy with formation of isolated proximal jejunal loops (Thiry-Vella loops). Animals were recovered for 10 days before harvesting at 4 6-h intervals (Zeitgeber times ZT3, ZT9, ZT15, and ZT21, where ZT0 is lights on; n = 6-8). SGLT1 expression was assessed in protein, and mRNA extracts of mucosa were harvested from both isolated loops (LOOP) and remnant jejunum (JEJ). RESULTS: Isolated loops were healthy but atrophic with minimal changes to villus architecture. A normal anticipatory rhythm was observed in Sglt1 transcription in both LOOP and JEJ, with the peak signal at ZT9 (2.7-fold, P < .001). Normal diurnal rhythms were also observed in the protein signal, with peak expression in both LOOP and JEJ at ZT9 to 15 (2.1-fold, P < .05). However, an additional more mobile polypeptide band was also observed in all LOOP samples but not in JEJ samples (61 kDa vs 69 kDa). Enzymatic deglycosylation suggested this to be deglycosylated SGLT1. CONCLUSION: The persistence of SGLT1 rhythmicity in isolated loops indicates that diurnal induction is independent of local luminal nutrient delivery, and it suggests a reliance on systemic entrainment pathways. However, local luminal signals may regulate glycosylation and, therefore, the posttranslational handling of SGLT1. SN - 1532-7361 UR - https://www.unboundmedicine.com/medline/citation/19231582/Diurnal_expression_of_the_rat_intestinal_sodium_glucose_cotransporter_1__SGLT1__is_independent_of_local_luminal_factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-6060(08)00696-X DB - PRIME DP - Unbound Medicine ER -