SGLT-5 Activators

SGLT-5 Activators encompass a selection of chemical compounds that indirectly increase the functional activity of SGLT-5, a protein implicated in the renal reabsorption of glucose. The mechanism of action begins with compounds like Phlorizin, an SGLT competitive inhibitor; by inhibiting glucose transport, it inadvertently induces a compensatory upregulation of SGLT-5 to maintain glucose reabsorption efficiency. Similarly, a series of SGLT2 inhibitors, including Dapagliflozin, Canagliflozin, Empagliflozin, Luseogliflozin, Ipragliflozin, Tofogliflozin, and Ertugliflozin, exert an off-target effect on SGLT-5. Their primary action on SGLT2 leads to an increased glucose excretion in urine, which in turn triggers a homeostatic response to enhance SGLT-5 activity, thereby indirectly augmenting the protein's role in glucose reuptake.

Further indirect activation is achieved with the dual SGLT1 and SGLT2 inhibitor, Sotagliflozin, which also modulates SGLT-5 activity by altering the dynamics of glucose absorption and prompting a compensatory increase in SGLT-5 function. Prodrugs like Remogliflozin etabonate and Sergliflozin etabonate, upon conversion to their active forms that inhibit SGLT2, similarly promote a compensatory enhancement of SGLT-5 activity. Lastly, Nateglinide, an antidiabetic agent that stimulates insulin secretion, may indirectly upregulate SGLT-5 activity. The presence of insulin is known to increase the expression and activity of SGLT transporters, suggesting that Nateglinide's role in insulin release could result in enhanced SGLT-5 activity through insulin-mediated pathways, completing the spectrum of activators that indirectly but effectively enhance the functional activity of SGLT-5 without directly interacting with the protein itself.