scholarly journals Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

2020 ◽  
Vol 21 (21) ◽  
pp. 7833
Author(s):  
Yi-Chou Hou ◽  
Cai-Mei Zheng ◽  
Tzung-Hai Yen ◽  
Kuo-Cheng Lu
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Tone ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Clinical Evidence ◽  
Sglt2 Inhibitor ◽  
Cardiac Protection ◽  
Glucose Transporter 2 ◽  
Glucose Reabsorption ◽  
Molecular Aspects

The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

scholarly journals Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia

2020 ◽  
Vol 21 (17) ◽  
pp. 6286
Author(s):  
Sanaa Sharari ◽  
Mohamad Abou-Alloul ◽  
Khalid Hussain ◽  
Faiyaz Ahmad Khan
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Poor Growth ◽  
Renal Tubular Cells ◽  
Glucose Transporter 2 ◽  
Compound Heterozygous Variants ◽  
Slc2a2 Gene

Accumulation of glycogen in the kidney and liver is the main feature of Fanconi–Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indels, splice site, and compound heterozygous variants have all been identified in SLC2A2 gene of FBS cases. Approximately 144 FBS cases with 70 different SLC2A2 gene variants have been reported so far. SLC2A2 encodes for glucose transporter 2 (GLUT2) a low affinity facilitative transporter of glucose mainly expressed in tissues playing important roles in glucose homeostasis, such as renal tubular cells, enterocytes, pancreatic β-cells, hepatocytes and discrete regions of the brain. Dysfunctional mutations and decreased GLUT2 expression leads to dysglycaemia (fasting hypoglycemia, postprandial hyperglycemia, glucose intolerance, and rarely diabetes mellitus), hepatomegaly, galactose intolerance, rickets, and poor growth. The molecular mechanisms of dysglycaemia in FBS are still not clearly understood. In this review, we discuss the physiological roles of GLUT2 and the pathophysiology of mutants, highlight all of the previously reported SLC2A2 mutations associated with dysglycaemia, and review the potential molecular mechanisms leading to dysglycaemia and diabetes mellitus in FBS patients.

SGLT-2 inhibitors: Ideal Remedy for Cardioprotection in Diabetes Mellitus.

2020 ◽  
Vol 13 ◽  
Author(s):  
Keshav Kumar ◽  
Tapan Behl ◽  
Arun Kumar ◽  
Sandeep Arora
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Transporter ◽  
Clinical Trial Data ◽  
Cardiac Complications ◽  
Cardiac Inflammation ◽  
First Line Therapy ◽  
Glucose Transporter 2 ◽  
Specific Medication ◽  
Hba1c Levels

Background: A chronic metabolic disease, diabetes mellitus (DM), is associated with various comorbidity due to cardiac complications that considerably decreasing the quality of life, but there is no specific medication for this. The recent developed drugs Sodium glucose transporter 2 inhibitors (SGLT2-Is), have action on diabetes as well as on kidney. Current research and studies have shown that SGLT2-Is attenuated the risk of cardiac complication associated with morbidity and hospitalization in diabetes patients. Introduction: Sodium glucose linked transporter 2 (SGLT2) receptors are mainly situated in proximal tubule of nephron. About 90% of glucose concentration is reabsorbed by these receptors in the nephron. The advanced remedy for the management of DM is SGLT2-Is which inhibit or lower the reabsorption of glucose. Objectives: The present review explores the mechanistic principle and the clinical trial data of SGLT2-Is which further support cardioprotective effects associated with these medications. Methods: The review collaborates PUBMED, Google Scholar and Research gate databases, which were explored using keywords and their combinations such as sodium glucose co-transporter 2 inhibitors, diabetes mellitus, cardioprotective effect, empagliflozin, canagliflozin, dapagliflozin and several others, to create an eclectic manuscript. Results: SGLT2-Is showed improvement in diabetes as well as in cardiac complications. These medications decreased HbA1c levels to control hyperglycemia. The mechanism of action of these drugs showed reduction in cardiac oxidative stress, cardiac apoptosis and cardiac inflammation. Besides, SGLT-2-Is showed improvement in cardiac structure and cardiac function. Conclusion: Anti-diabetic drugs, SGLT2-Is have a protective effect against cardiac complications. This indicates that these medication could become first line therapy for cardiac patients with DM.

scholarly journals Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic Nephropathy

2017 ◽  
Vol 29 (2) ◽  
pp. 434-448 ◽  
Author(s):  
Liad Hinden ◽  
Shiran Udi ◽  
Adi Drori ◽  
Asaad Gammal ◽  
Alina Nemirovski ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Brush Border Membrane ◽  
Glucose Transporter ◽  
Interstitial Fibrosis ◽  
Proximal Tubule Cell ◽  
Functional Changes ◽  
Glucose Transporter 2 ◽  
Cannabinoid 1 Receptor ◽  
Glucose Reabsorption ◽  
Altered Glucose

Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2 expression, affected the dynamic translocation of GLUT2 to the brush border membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and ameliorate DN. These findings may support the rationale for the clinical testing of peripherally restricted CB1R antagonists or the development of novel renal-specific GLUT2 inhibitors against DN.

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 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 Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Habib Yaribeygi ◽  
Mina Maleki ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Physical Activity ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Physical Inactivity ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Sedentary Lifestyle ◽  
Negative Impact ◽  
Health It ◽  
Lower Physical Activity

The modern lifestyle has a negative impact on health. It is usually accompanied by increased stress levels and lower physical activity, which interferes with body homeostasis. Diabetes mellitus is a relatively common metabolic disorder with increasing prevalence globally, associated with various risk factors, including lower physical activity and a sedentary lifestyle. It has been shown that sedentary behavior increases the risk of insulin resistance, but the intermediate molecular mechanisms are not fully understood. In this mechanistic review, we explore the possible interactions between physical inactivity and insulin resistance to help better understand the pathophysiology of physical inactivity-dependent insulin resistance and finding novel interventions against these deleterious pathways.

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