The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing

Mol Metab. 2012 Dec 7;2(1):47-53. doi: 10.1016/j.molmet.2012.11.003. eCollection 2012.


Portal vein glucose sensors detect variations in glycemia to induce a nervous signal that influences food intake and glucose homeostasis. Previous experiments using high infusions of glucose suggested a metabolic sensing involving glucose transporter 2 (GLUT2). Here we evaluated the afferent route for the signal and candidate molecules for detecting low glucose fluxes. Common hepatic branch vagotomy did not abolish the anorectic effect of portal glucose, indicating dorsal transmission. GLUT2-null mice reduced their food intake in response to portal glucose signal initiated by protein-enriched diet. A similar response of Trpm5-null mice and portal infusions of sweeteners also excluded sugar taste receptors. Conversely, infusions of alpha-methylglucose, but not 3-O-methylglucose, decreased food intake, while phlorizin prevented the effect of glucose. This suggested sensing through SGLT3, which was expressed in the portal area. From these results we propose a finely tuned dual mechanism for portal glucose sensing that responds to different physiological conditions.

Keywords: (3-O-MDG), 3-O-methyl-d-glucopyranose; (5-HT), 5-hydroxytryptamin/serotonin; (EGP), endogenous glucose production; (G6PC), glucose-6-phosphatase catalytic subunit; (GAPDH), glyceraldehyde-3-phosphate dehydrogenase; (GFAP), glial fibriallary acidic protein; (GLP1), glucagon-like peptide 1; (GLUT), glucose transporter; (PED), protein-enriched diet; (PGP9.5), protein gene product 9.5; (SED), starch-enriched diet; (SGLT), sodium glucose co-transporter; (Trpm5), transient receptor potential melastin 5; (αMDG), α-methylglucopyranoside; Food intake; Glucose metabolism; Glucose sensing; Peripheral nervous signal; Portal vein; SGLTs.