Higher renal gluconeogenesis may explain similar hyperglycemia despite lower SGLT2 expression and higher glucosuria in diabetic NHE3-KO versus wild-type mice; stronger SGLT1 engagement could have affected kidney weight and GFR responses.
Sodium-glucose co-transporter (SGLT)-2 inhibitors and dual SGLT-1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin-independent mechanisms.
We identified a novel mechanism of acute hyperglycemia-induced hyperfiltration wherein increases in luminal glucose at the macula densa upregulate the expression and activity of NOS1 <i>via</i> SGLT1, blunting the TGF response and promoting glomerular hyperfiltration.
Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion.