title: Foregut exclusion disrupts intestinal glucose sensing and alters portal nutrient and hormonal milieu.
abstract: The antidiabetes effects of Roux-en-Y gastric bypass (RYGB) are well-known, but the underlying mechanisms remain unclear. Isolating the proximal small intestine, and in particular its luminal glucose sensors, from the nutrient stream has been proposed as a critical change, but the pathways involved are unclear. In a rodent model, we tested the effects of isolating and then stimulating a segment of proximal intestine using glucose analogs to examine their impact on glucose absorption (Gabsorp) and hormone secretion after a glucose bolus into the distal jejunum. Analogs selective for sodium-glucose cotransporter (SGLT) family members and the sweet taste receptor were tested, and measurements of the portosystemic gradient were used to determine Gabsorp and hormone secretion, including GLP-1. Proximal intestinal isolation reduced Gabsorp and GLP-1 secretion. Stimulation of the glucose-sensing protein SGLT3 increased Gabsorp and GLP-1 secretion. These effects were abolished by vagotomy. Sweet taste receptor stimulation only increased GLP-1 secretion. This study suggests a novel role for SGLT3 in coordinating intestinal function, as reflected by the concomitant modulation of Gabsorp and GLP-1 secretion, with these effects being mediated by the vagus nerve. Our findings provide potential mechanistic insights into foregut exclusion in RYGB and identify SGLT3 as a possible antidiabetes therapeutic target.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA Harvard Medical School, Boston, MA.
authors.forename: Atanu
authors.initials: A
authors.lastname: Pal
authors.affiliation: Harvard Medical School, Boston, MA Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA.
authors.forename: David B
authors.initials: DB
authors.lastname: Rhoads
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA Harvard Medical School, Boston, MA atavakkoli@partners.org.
authors.forename: Ali
authors.initials: A
authors.lastname: Tavakkoli
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051247:Sodium-Glucose Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C495676:Slc5a1 protein, rat; D051247:Sodium-Glucose Transport Proteins; D051269:Sodium-Glucose Transporter 1; D005947:Glucose