Sodium-glucose cotransporter 1 (SGLT1) (SGLT1)

Intestinal nutrient-sensing cells, primarily enteroendocrine L-cells and K-cells, are specialized cells in the gut epithelium that detect luminal nutrients to regulate metabolic homeostasis. The primary molecular sensor for luminal glucose in these cells is the Sodium-glucose cotransporter 1 (SGLT1), which facilitates glucose entry and triggers the secretion of incretin hormones such as Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) (Gribble & Reimann, 2019, PubMed: 30649637). These hormones play a critical role in the incretin effect, enhancing insulin secretion from the pancreas in response to oral glucose intake. In addition to SGLT1, sweet taste receptors (TAS1R2/TAS1R3) may also contribute to the sensing of luminal sugars (Gorboulev et al., 2012, PubMed: 23403053). Pharmacological targeting of this system, particularly through SGLT1 inhibitors, aims to treat Type 2 diabetes and obesity by delaying glucose absorption and augmenting the endogenous release of GLP-1 (Rieg & Vallon, 2018, PubMed: 30115801). However, therapeutic challenges include gastrointestinal side effects like diarrhea and flatulence, which result from the osmotic effects of unabsorbed glucose reaching the large intestine.

Other names

SLC5A1Sodium/glucose cotransporter 1Enteroendocrine glucose sensorSolute carrier family 5 member 1

SGLT1 inhibitors block the active transport of glucose from the intestinal lumen into enterocytes, thereby slowing glucose absorption and increasing the delivery of glucose to the distal small intestine, which triggers the release of GLP-1 and PYY from L-cells.