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.
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.