Active sugar transport in health and disease

Abstract

Secondary active glucose transport occurs by at least four members of the SLC5 gene family. This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption. Genetics disorders of SGLTs include GlucoseGalactose Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes.

GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-βl and plasma glucose concentration

“…There is growing evidence that targeting SGLT-mediated renal glucose transport using phlorizin-like inhibitors may be useful in treating diabetes [32]. Two sodium-dependent transporters are produced in the kidney: the bulk of the filtered glucose is reabsorbed in the S1 segment by the lowaffinity, high-capacity transporter, SGLT2; whereas the high-affinity, low-capacity transporter, SGLT1, scavenges the remaining glucose more distally (reviewed in [17]).…”

Luseogliflozin and other sodium-glucose cotransporter 2 inhibitors: no enemy but time?

“…Under normal conditions,~180 g of glucose are filtered by the kidney glomerulus per day, and virtually the entire amount is reabsorbed in the proximal tubule [6]. The absorption of glucose in the small intestine and the reabsorption in the kidney occurs passively by glucose transporters (GLUTs) and actively by sodium-glucose cotransporters (SGLTs) [7].…”

“…The SGLT2 and GLUT2 are expressed predominantly in cells of the proximal tubule of the kidney on the S1 segment, where the majority of glucose reabsorption (~90%) is accomplished [7]. Meanwhile,~10% is reabsorbed in the S3 regimen, where SGLT1 and GLUT1 are located [7].…”

“…Meanwhile,~10% is reabsorbed in the S3 regimen, where SGLT1 and GLUT1 are located [7]. Glycosuria will appear if the filtered glucose exceeds the glucose threshold of 180 mg/dl or the filtered glucose load exceeds 375 mg/min or if the renal reabsorptive capacity is reduced [4,5].…”

“…Indeed, the safety and efficacy of these agents in T2DM have been thoroughly studied, both in randomised controlled trials and in systematic reviews and meta-analyses [7,[10][11][12][13]. Vasilakou et al [10] have recently demonstrated that the use of canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, tofogliflozin, ertugliflozin and remogliflozin was accompanied by a significant reduction in HbA 1c levels compared with placebo as monotherapy (mean difference -0.79%) or as add-on treatment (mean difference -0.61%), or against active comparator as add-on treatment (mean difference -0.16%).…”