Putative tissue location and function of the SLC5 family member SGLT3

Sodium glucose transporter 3 (SGLT3) has attracted interest because of its putative role as a glucose sensor, rather than a sugar transporter, in contrast to its SGLT1 and SGLT2 co-family members. Significant progress has been made in characterizing the electrophysiological properties in vitro of the single human SGLT3 isoform and the two mouse isoforms, SGLT3a and SGLT3b. Although early reports indicated SGLT3 expression in the small intestinal myenteric and submucosal neurones, hypothalamic neurones, portal vein, and kidney, a lack of reliable antibodies has left unanswered its exact tissue and cellular localization. Several hypotheses for a role of SGLT3 in glucose sensing, gastric emptying, GLP-1 release, and post-Roux en-Y gastric bypass remodelling have been explored, but so far there is only limited and indirect supportive evidence using non-specific agonists/antagonists, but with no firm conclusions. There are no published or available data in knockout animals and translation is difficult because of its different isoforms in human versus rodent, as well as a lack of selective agonists or antagonists, all making SGLT3 challenging to study. However, its unique electrophysiological properties, ubiquitous expression at the mRNA level, enrichment in the small intestine, and potential, but uncertain, physiological role demand more attention. The purpose of this overview and review of SGLT3 biology is to provide an update, highlight the gaps in our knowledge, and try to signpost potential ways forward to define its likely function in vivo.

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