Probable glucose sensor protein SLC5A4 (SLC5A4)

SLC5A4 (Probable glucose sensor protein SLC5A4, commonly termed SGLT3) is a transmembrane protein belonging to the solute carrier family 5 (sodium-glucose cotransporters)[1][6][9]. Unlike SGLT1 and SGLT2, which actively transport glucose across membranes, SLC5A4 does not transport glucose but acts as a molecular sensor, generating Na+-dependent, phlorizin-sensitive depolarization in response to extracellular glucose[1][3][4][6]. It is expressed chiefly in cholinergic neurons of the gut, as well as in skeletal muscle, and may modulate neuronal and muscular responses to local glucose levels[1]. SLC5A4 is genetically associated with small-cell lung cancer and attention-deficit/hyperactivity disorder (ADHD) through rare sequence variants[1][3][4][5]. While miglitol can indirectly activate gut hormone secretion through SLC5A4-dependent mechanisms, SLC5A4 is not a primary therapeutic target for currently marketed drugs[1]. It serves more as a physiological sensor than a transporter, and is not known to play a role in classical glucose reabsorption or metabolism[6][4].\n\nNote: SLC5A4/SGLT3 should not be confused with SGLT1 (SLC5A1) or SGLT2 (SLC5A2), which are established targets for diabetes therapeutics, as SLC5A4 does not transport glucose but senses it[6].

Other names

SGLT3SAAT1DJ90G24.4Sodium/glucose cotransporter 3Solute carrier family 5 member 4

For miglitol: Activation of enterochromaffin cells via glucose sensing to enhance glucagon-like peptide 1 (GLP-1) secretion through parasympathetic signaling (SGLT3-dependent). For phlorizin: Inhibition of glucose-induced depolarization/current via binding to SGLT3 sensor channel. For DNJ: Agonist action, stimulates sodium current/depolarization via SGLT3.