SGLT2 inhibition reduces cellular senescence in the diabetic kidney by promoting ketone body‐induced NRF2 activation

2021 ◽  
Author(s):  
Mi Na Kim ◽  
Joon Ho Moon ◽  
Young Min Cho
Keyword(s):  
Cellular Senescence ◽  
Ketone Body ◽  
Diabetic Kidney ◽  
Nrf2 Activation ◽  
Sglt2 Inhibition ◽  
In The Diabetic Kidney

scholarly journals SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition

2020 ◽  
Vol 32 (3) ◽  
pp. 404-419.e6 ◽  
Author(s):  
Issei Tomita ◽  
Shinji Kume ◽  
Sho Sugahara ◽  
Norihisa Osawa ◽  
Kosuke Yamahara ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Ketone Body ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Sglt2 Inhibition

scholarly journals SGLT2 Inhibition in the Diabetic Kidney—From Mechanisms to Clinical Outcome

2017 ◽  
Vol 12 (4) ◽  
pp. 700-710 ◽  
Author(s):  
Erik J.M. van Bommel ◽  
Marcel H.A. Muskiet ◽  
Lennart Tonneijck ◽  
Mark H.H. Kramer ◽  
Max Nieuwdorp ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Diabetic Kidney ◽  
Sglt2 Inhibition ◽  
In The Diabetic Kidney

Structural and Functional Alterations in the Diabetic Kidney

2015 ◽  
pp. 67-81 ◽  
Author(s):  
Carl Erik Mogensen ◽  
Ruth �sterby
Keyword(s):  
Diabetic Kidney ◽  
In The Diabetic Kidney

scholarly journals Do Tubular Changes in the Diabetic Kidney Affect the Susceptibility to Acute Kidney Injury?

2014 ◽  
Vol 127 (1-4) ◽  
pp. 133-138 ◽  
Author(s):  
Volker Vallon
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Diabetic Kidney ◽  
In The Diabetic Kidney

scholarly journals The Renoprotective Actions of Peroxisome Proliferator-Activated Receptors Agonists in Diabetes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
M. C. Thomas ◽  
K. A. Jandeleit-Dahm ◽  
C. Tikellis
Keyword(s):  
Cardiovascular Effects ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Oral Hypoglycaemic Agents ◽  
Diabetic Kidney ◽  
Critical Pathways ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
In The Diabetic Kidney

Pharmaceutical agonists of peroxisome proliferator-activated receptors (PPARs) are widely used in the management of type 2 diabetes, chiefly as lipid-lowering agents and oral hypoglycaemic agents. Although most of the focus has been placed on their cardiovascular effects, both positive and negative, these agents also have significant renoprotective actions in the diabetic kidney. Over and above action on metabolic control and effects on blood pressure, PPAR agonists also appear to have independent effects on a number of critical pathways that are implicated in the development and progression of diabetic kidney disease, including oxidative stress, inflammation, hypertrophy, and podocyte function. This review will examine these direct and indirect actions of PPAR agonists in the diabetic kidney and explore recent findings of clinical trials of PPAR agonists in patients with diabetes.

scholarly journals Glucose and glycogen in the diabetic kidney: Heroes or villains?

EBioMedicine ◽  
2019 ◽  
Vol 47 ◽  
pp. 590-597 ◽  
Author(s):  
Mitchell A. Sullivan ◽  
Josephine M. Forbes
Keyword(s):  
Diabetic Kidney ◽  
In The Diabetic Kidney

Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes

2011 ◽  
Vol 300 (2) ◽  
pp. E287-E295 ◽  
Author(s):  
Dongjuan Zhang ◽  
Hang Yang ◽  
Xiaomu Kong ◽  
Kang Wang ◽  
Xuan Mao ◽  
...  
Keyword(s):  
Ketone Body ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Ketone Bodies ◽  
Proximal Tubule Cell ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Proteomic Approach ◽  
Body Production

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. To date, the molecular mechanisms of DN remain largely unclear. The present study aimed to identify and characterize novel proteins involved in the development of DN by a proteomic approach. Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice. Consistently, the activity of HMGCS2 in kidneys and 24-h urinary excretion of the ketone body β-hydroxybutyrate (β-HB) were significantly increased in db/db mice. Immunohistochemistry, immunofluorescence, and real-time PCR studies further demonstrated that HMGCS2 was highly expressed in renal glomeruli of db/db mice, with weak expression in the kidneys of control mice. Because filtered ketone bodies are mainly reabsorbed in the proximal tubules, we used RPTC cells, a rat proximal tubule cell line, to examine the effect of the increased level of ketone bodies. Treating cultured RPTC cells with 1 mM β-HB significantly induced transforming growth factor-β1 expression, with a marked increase in collagen I expression. β-HB treatment also resulted in a marked increase in vimentin protein expression and a significant reduction in E-cadherin protein levels, suggesting an enhanced epithelial-to-mesenchymal transition in RPTCs. Collectively, these findings demonstrate that diabetic kidneys exhibit excess ketogenic activity resulting from increased HMGCS2 expression. Enhanced ketone body production in the diabetic kidney may represent a novel mechanism involved in the pathogenesis of DN.

scholarly journals Interacting hypoxia and endothelin in the diabetic kidney: therapeutic options

2018 ◽  
Vol 314 (5) ◽  
pp. F699-F701
Author(s):  
Samuel N. Heyman ◽  
Mogher Khamaisi ◽  
Zaid Abassi
Keyword(s):  
Therapeutic Options ◽  
Diabetic Kidney ◽  
In The Diabetic Kidney
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