Sodium-dependent glucose transporter protein as a potential therapeutic target for improving glycemic control in diabetes

Abstract

Glucose is transported across the cell membrane by two different types of glucose transporters: glucose-facilitated transporters and sodium-dependent glucose transport (SGLT) proteins. Regulation of SGLT activity (namely, inhibition of SGLT1 and SGLT2 activity and stimulation of SGLT3 activity) represents a potential means of managing hyperglycemia and diabetes, thus preventing complications of diabetes. The purpose of the present review is to discuss the role of SGLT proteins in the pathophysiology of diabetes and to describe the mechanisms by which these transporters may be used for glycemic control and the treatment of diabetes. The regulatory processes involved in SGLT-mediated glucose uptake are also described briefly. This information provides new insight into the complementary mechanisms involved in the regulation of SGLT-mediated glucose transport as well as a basis for further investigation.

Effect of Insulin‐Induced Hypoglycaemia on theCentral Nervous System: Evidence from Experimental Studies

“…Another example of a mainly intracellular localised glucose transporter is SGLT1 . Similar to GLUT4, SGLT1 activity is, at least in part, regulated by translocation to the plasma membrane and this trafficking is regulated by protein kinases A and C, as studied and discussed elsewhere . Insulin has been shown to increase rat intestinal glucose absorption in vitro and in vivo .…”

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

“…GLUT-1 transporters in mature and fully differentiated BBB endothelium are heterogeneously distributed with studies reporting higher luminal to abluminal ratio in human brain microvessels [60,61], while the opposite holds true in rats and other species [62,63]. This heterogeneity correlates to the variable energy demands, cerebral glucose utilization and maintenance of normal glucose level [64,65] with reports suggesting an increase in their local densities, due to increase in local cerebral glucose utilization [53]. More specifically, increased glucose transport across BBB correlated with increased luminal density of GLUT-1.…”

EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors

“…SGLT1 is an active glucose transporter that relies on extracellular sodium concentration to transport glucose into cells independent of glucose concentration . SGLT1 plays a critical role in glucose absorption and retention in the body . One of the hallmarks of cancer is that cancer cells exhibit altered energy metabolism, that is, cancer cells consume higher amounts of nutrients and energy substrates than their normal counterparts .…”