Dapagliflozin in patients with type 2 diabetes mellitus

Abstract

Mechanism of action SGLT2 mediates approximately 90% of active renal glucose reabsorption in the S1 segment of early proximal tubule of the kidney [Vallon et al. 2011]. Dapagliflozin is a selective and reversible inhibitor of SGLT2, leading to a significant reduction in glucose reabsorption and decrease of serum glucose concentration in an insulin-independent manner [Balakumar et al. 2014]. Dapagliflozin also improves insulin sensitivity but enhances endogenous glucose production in patients with T2DM [Merovci et al. 2014; Mudaliar et al. 2014]. The reduction in glucose reabsorption by dapagliflozin has been associated

Effect of Combined Treatment With Insulin and Other Hypoglycemic Drugs on 5'amp-Activated Protein Kinase Activity in Leucocytes of Patients With Diabetes Mellitus

“…With T2D and obesity, its activity decreases, and the activity of protein kinases mTORC1/p70S6K (mammalian target of rapamycin complex 1/ribosomal protein S6 kinase beta-1) increases, leading to phosphorylation of insulin receptor substrate-1 and insulin resistance [24]. The effect of hypoglycemic drugs, such as metformin, is associated with the activation of AMPK, and dapagliflozin -with the inhibition of the sodium/glucose cotransporter 2 (SGLT2), responsible for the reabsorption of glucose in the proximal tubules of the kidney [25].…”

Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors

“…However, the underlying mechanisms are not clear yet. On the other hand, these drugs should be carefully administrated in patients treated with diuretics to avoid hypovolemia and hypotension [7,20]. Interestingly, in the EMPA-REG, in which 43.7% of the study population were on diuretics, empagliflozin administration was associated with a small (statistically insignificant) increase in stroke incidence, which is speculated to be related to increase diuresis-associated hypovolemia and compromised cerebral blood supply.…”

Empagliflozin: an exciting prospect in the treatment of diabetes

“…SGLT's are large family of membrane proteins that transport glucose in brush border of intestinal epithelium and proximal renal tubules using electrochemical sodium gradient as the source of energy generated by Na+-K+ adenosine triphosphatase. [4][5][6][7] SGLT-2 is a high capacity low affinity Na+ coupled glucose transporter in apical part of early proximal convoluted tubule, and it is responsible for 90% of glucose reabsorption. In contrast SGLT-1 located in distal PCT reabsorbs the remaining 10% glucose which escaped reabsorption by SGLT-2.…”