Mechanistic evaluation of the effect of sodium‐dependent glucose transporter 2 inhibitors on delayed glucose absorption in patients with type 2 diabetes mellitus using a quantitative systems pharmacology model of human systemic glucose dynamics

2020 ◽  
Vol 41 (8-9) ◽  
pp. 352-366
Author(s):  
Kazumi Mori‐Anai ◽  
Yoshihiko Tashima ◽  
Tomohisa Nakada ◽  
Yoshinobu Nakamaru ◽  
Takayuki Takahata ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Glucose Transporter ◽  
Glucose Absorption ◽  
Systems Pharmacology ◽  
Quantitative Systems Pharmacology ◽  
Glucose Transporter 2 ◽  
Sodium Dependent ◽  
Glucose Dynamics

scholarly journals A new trend in the treatment of type 2 diabetes mellitus with the use of sodium-dependent glucose transporter-2 inhibitors

2014 ◽  
Vol 60 (4) ◽  
pp. 60-64
Author(s):  
V G Kadzharyan ◽  
N I Kapshitar’
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Transporter ◽  
Reverse Flow ◽  
Selective Inhibition ◽  
Antidiabetic Therapy ◽  
Glucose Transporter 2 ◽  
Sodium Dependent

Insulin is traditionally the main application point on which all methods for the management of type 2 diabetes mellitus are targeted. One of the new strategies for the treatment of this pathology utilizes sodium-dependent glucose transporter-2 (SGLT-2) inhibitors transforms this approach making kidneys the new point of application of antidiabetic therapy. SGLT-2 functions as a tunnel built into the epithelial wall of the initial segment of the proximal tubules in the nephron. When the channel is open, glucose is filtered into primary urine and can be reabsorbed in the proximal tubule. Based on this observation, the pharmaceutical companies began to search for the chemical substances that could be used to close the SGLT-2 tunnels and thereby interfere with the reverse flow of glucose from urine to blood, i.e. stimulate glycosuria. During the last decade, a few alternative molecules have been synthesized capable of selective inhibition of SGLT-2. At present, two of them, dapagliflozin and canagliflozin, are approved for the clinical application.

scholarly journals Studies of Genetic Variability of the Glucose Transporter 2 Promoter in Patients with Type 2 Diabetes Mellitus

2001 ◽  
Vol 86 (5) ◽  
pp. 2181-2186 ◽  
Author(s):  
Ann M. Møller ◽  
Niels M. Jensen ◽  
Julie Pildal ◽  
Thomas Drivsholm ◽  
Knut Borch-Johnsen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Variability ◽  
Glucose Transporter ◽  
Glucose Transporter 2

scholarly journals Inhibitors of the sodium-glucose transporter type 2 and new possibilities for managing vascular age in patients with type 2 diabetes mellitus

2021 ◽  
pp. 228-236
Author(s):  
I. Sh. Khalimov ◽  
Yu. Ye. Rubtsov ◽  
V. V. Salukhov ◽  
P. V. Agafonov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Glucose Transporter ◽  
Vascular Stiffness ◽  
Vascular Aging ◽  
Glucose Transporter 2 ◽  
Vascular Age

The article discusses the pathophysiological mechanisms of the development of vascular aging as a combination of the influence on the  body of  genetic, environmental, regulatory, metabolic and other factors causing biochemical, enzymatic and cellular changes in the arterial vascular bed. The concept of “early vascular aging” and “healthy vascular aging” is defined depending on the ratio of the biological and chronological age of the vessels. The role of diabetes mellitus in increasing vascular stiffness, early vascular aging, as well as the  progression of  atherosclerotic cardiovascular diseases and their complications is considered in detail. Approaches to multifactorial management of vascular age in patients with type 2 diabetes (lifestyle modification with strategy of aggressive treatment of modifiers of atherosclerosis, rejection of bad habits, adherence to dietary recommendations and the use of modern organo- and vasoprotective antidiabetic drugs) are revealed. The mechanism of realization of vasoprotective effects of inhibitors of sodium-glucose transporter-2 (iNGLT-2) is described in detail. The results of completed large random ized trials EMPA-REG Outcome and EMPA-REG BP of the most studied representative of the IGLT-2 group, empagliflozin, are presented. It has been shown that due to their glucose and natriuretic effects, the ability to reduce body weight and blood pressure, improve myocardial metabolism and bioenergetics, decrease the activity of the sympathetic nervous system, as well as positive effects on vascular stiffness, NGLT-2 inhibitors are the drugs of choice in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. This makes it possible to widely use this group of drugs for managing the vascular age of patients and represents a new opportunity in the prevention of vascular aging in T2DM. 

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