scholarly journals Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes

Diabetes Care ◽  
2013 ◽  
Vol 36 (10) ◽  
pp. 3169-3176 ◽  
Author(s):  
R. A. DeFronzo ◽  
M. Hompesch ◽  
S. Kasichayanula ◽  
X. Liu ◽  
Y. Hong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

Mixed-effects modelling to quantify the effect of empagliflozin on renal glucose reabsorption in patients with type 2 diabetes

2016 ◽  
Vol 18 (3) ◽  
pp. 241-248 ◽  
Author(s):  
J. Mondick ◽  
M. Riggs ◽  
T. Sasaki ◽  
A. Sarashina ◽  
U. C. Broedl ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mixed Effects ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

Targeting Renal Glucose Reabsorption for the Treatment of Type 2 Diabetes Mellitus Using the SGLT2 Inhibitor Dapagliflozin

2012 ◽  
Vol 124 (4) ◽  
pp. 62-73 ◽  
Author(s):  
Serge A. Jabbour ◽  
Jean M. Whaley ◽  
Mark Tirmenstein ◽  
Simon M. Poucher ◽  
Timothy P. Reilly ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sglt2 Inhibitor ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

scholarly journals New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes—A Review

2021 ◽  
Vol 23 (1) ◽  
pp. 356
Author(s):  
Christo J. F. Muller ◽  
Elizabeth Joubert ◽  
Nireshni Chellan ◽  
Yutaka Miura ◽  
Kazumi Yagasaki
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Tyrosine Phosphatase ◽  
Dietary Exposure ◽  
Therapeutic Effects ◽  
Glucose Reabsorption ◽  
Flavone Derivatives ◽  
Renal Glucose Reabsorption

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D.

Sign in / Sign up

Export Citation Format

Share Document