Putative tissue location and function of the SLC5 family member SGLT3

What is the topic of this review? This review summarizes the evidence on the localization, electrophysiological properties, agonist specificity and putative physiological role of sodium-glucose transporter 3 (SGLT3). What advances does it highlight? Published information is reviewed in some detail by comparing human and rodent isoforms, as well as advances in testing hypotheses for the physiological role of SGLT3 as a glucose sensor or incretin release mediator. We provide a critical overview of available published data and discuss a putative functional role for SGLT3 in human and mouse physiology. 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 co-family members SGLT1 and SGLT2. 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, glucagon-like peptide-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, 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 of which make 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.