Foregut exclusion disrupts intestinal glucose sensing and alters portal nutrient and hormonal milieu
Open accessAbstract
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.
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STR-dependent release of GLP-1 and GLP-2 is detected at higher concentrations in the portal and lymphatic circulation than the systemic circulation in rodents.
“and STR-dependent release of both GLP-1 and GLP-2 is detected at higher concentrations in the portal and lymphatic circulation than the systemic circulation in rodents (28,53).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [53]
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- Authors
- Pal, A., Rhoads, D. B., & Tavakkoli, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Tavakkoli, Ali
- ORCID
- Tavakkoli, Ali
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-01-09
- Volume
- 64
- Issue
- 6
- Pages
- 1941-1950
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4439569
- OpenAlex
- W1985132605
- Cited by
- 29
- References
- 33
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 1
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 DK084064 (AT))
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Roux-en-Y gastric bypass, glucose absorption, GLP-1 secretion, sweet taste receptor, vagus nerve, vagotomy, portosystemic pressure gradient, bariatric surgery
- MeSH terms
- Animals, Glucose, Glucose Tolerance Test, Intestinal Mucosa, Male, Rats, Sprague-Dawley, Sodium-Glucose Transport Proteins, Sodium-Glucose Transporter 1, Rats, Real-Time Polymerase Chain Reaction, In Vitro Techniques
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