SGLT-3b Activators

Chemical activators of SGLT-3b include a variety of compounds that engage the protein in different ways, each facilitating its transport activity. Phlorizin, a competitive inhibitor known for its interactions with sodium-glucose co-transporters, can paradoxically activate SGLT-3b by competing with glucose for binding sites, which can lead to an increase in transporter activity as the protein attempts to compensate for the competitive binding. Similarly, methyl-α-D-glucopyranoside, due to its structural resemblance to glucose, activates SGLT-3b by mimicking the natural activation mechanism of the protein. This binding can trigger a conformational change, prompting SGLT-3b to increase its transport function.

Direct substrates such as glucose itself are pivotal for the activation of SGLT-3b. By binding to the transporter, glucose induces a conformational shift that inherently activates the glucose transport function of SGLT-3b. This interaction is the primary and most direct method of activation. Moreover, sulfonylureas like chlorpropamide, tolbutamide, glyburide, glimepiride, and glibenclamide can enhance SGLT-3b activity. These chemicals may interact with SGLT-3b to alter its conformation or sensitivity to glucose, resulting in an increase in the transporter's activity. Glycopyrrolate, although primarily targeting different systems, can indirectly activate SGLT-3b by modulating cellular ionic balances, which may favor the activation of the transporter. Flavonoids and isoflavones, represented by quercetin, genistein, and daidzein, activate SGLT-3b by influencing the lipid milieu of the transporter or by affecting the phosphorylation state of proteins that regulate the transport activity. These compounds can lead to an upregulation of SGLT-3b's glucose transport function by promoting an environment conducive to the transporter's optimal activity.