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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Sodium glucose cotransporter 2 inhibition in the diabetic kidney: an update

Aleksandra Novikov1, Volker Vallon

  • 1aDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla bVeterans Affairs San Diego Healthcare System, San Diego cDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.

Current Opinion in Nephrology and Hypertension
|November 18, 2015
PubMed
Abstract

Insights

Sodium glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose by reducing kidney reabsorption. New findings reveal SGLT2

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium glucose cotransporter 2 (SGLT2) is primarily responsible for glucose reabsorption in the kidneys.
  • SGLT2 inhibitors are approved antihyperglycemic drugs with promising therapeutic potential.
  • Despite clinical success, the full scope of SGLT2 function and inhibition effects requires further elucidation.

Purpose of the Study:

  • To review and synthesize current understanding of SGLT2 expression, function, and the multifaceted effects of SGLT2 inhibition.
  • To explore emerging roles and potential therapeutic applications of SGLT2 inhibitors beyond glycemic control.

Main Methods:

  • Localization of SGLT2 expression in human kidney proximal tubules using validated antibodies.
  • Investigation of SGLT2 upregulation in diabetic murine models.
  • Analysis of SGLT1-mediated glucose reabsorption during SGLT2 inhibition.
  • Examination of SGLT2 expression and function in pancreatic alpha cells.
  • Assessment of SGLT2 inhibition effects on glomerular filtration rate and renal hemodynamics in diabetic patients.

Main Results:

  • SGLT2 is localized to the proximal tubule brush border and upregulated in diabetes.
  • SGLT1 accounts for significant residual glucose reabsorption during SGLT2 inhibition.
  • SGLT2 inhibition in pancreatic alpha cells stimulates glucagon secretion.
  • SGLT2 inhibition lowers glomerular filtration rate in hyperfiltering diabetic patients.
  • Emerging evidence suggests SGLT2 inhibition may mitigate renal medullary hypoxia, ketoacidosis, and offer nephroprotective benefits.
  • Potential roles in inhibiting renal gluconeogenesis, reducing cardiovascular mortality, and cancer therapy are indicated.

Conclusions:

  • Current findings enhance the understanding of SGLT2 biology and the mechanisms of SGLT2 inhibitors.
  • The data have significant implications for clinical practice and the interpretation of ongoing clinical trials.
  • Further research is warranted to fully explore the long-term safety and cardiovascular benefits of SGLT2 inhibitors.

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