GLUCOSE UPTAKE INHIBITION
The creation of novel medicines to improve glycemic control and diabetes management is a great opportunity to target sodium-dependent glucose transport (SGLT) proteins. SGLT1 and SGLT2 are two different isoforms of SGLT that serve to distinguish both of them [Citation3,Citation4]. In kidneys, SGLT plays an important role in glucose homeostasis by filtering and reabsorbing glucose from nearby tissues. Every day, the kidneys filter about 180 g of glucose [Citation5]. Since SGLT1 is a high-affinity transporter, low volume that is situated in the intestine and kidney and secretes about 10% of glucose from the distal tubule. Moreover, SGLT2 is a low-affinity transporter, high-volume that is situated in the proximal convoluted tubule(PCT) and secretes about 90% of reabsorbing glucose filtered by the kidney [Citation6,Citation7]. An attractive treatment method for hyperglycemia is to stop renal glucose reabsorption by blocking SGLT2.
Under normal physiological conditions, SGLT2ʹs primary function is to reabsorb glucose that has been filtered by the renal glomeruli. Sodium-glucose cotransporter 2 (SGLT2) absorbs roughly 90% of the kidney’s glucose and reabsorbed glucose transferred to plasma through GLUT-2 while sodium-glucose cotransporter 1(SGLT1), absorbs a remaining portion of glucose and then transferred to plasma by GLUT-1()
Figure 1. Describes the Glucose renal reabsorption process and the mechanism of SGLT2 inhibitors:
In GIT(gastrointestinal tract), SGLT1 is a vital transporter for glucose uptake but the effect in kidneys is less significant whereas SGLT2 serves as important transporter (reabsorbs 90% glucose) in kidneys which causes hyperglycemia in diabetes mellitus. Thus, this transporter (SGLT2) has gained interest in the treatment for the T2DM. Especially in hypoglycemic patients SGLT2 inhibitors oppose the effects of SGLT2 transporter, thereby increasing glucosuria and decreasing serum glucose levels. SGLT2 inhibitors have been demonstrated to improve CVS outcomes and provided much-needed advantages for type −2 diabetes mellitus. Full article: Sodium-glucose transporter (SGLT2) inhibition: A potential target for treatment of type-2 Diabetes Mellitus with Natural and Synthetic compounds (tandfonline.com)
2.) SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects
3.) The Mechanisms and Therapeutic Potential of SGLT2 Inhibitors in Diabetes Mellitus
5.) SGLT2 inhibition — a novel strategy for diabetes treatment
6.) SGLT2 Inhibitors: Physiology and Pharmacology
7.) An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus
8.) SGLT2 Inhibitors: A New Emerging Therapeutic Class in the Treatment of Type 2 Diabetes Mellitus
9.) Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus
10.) The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus