Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit

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Updated: Jul 4, 2026

Transcutaneous Assessment of Renal Function in Conscious Rodents
07:18

Transcutaneous Assessment of Renal Function in Conscious Rodents

Published on: March 26, 2016

Ildikó Toma1, Jung Julie Kang, Arnold Sipos

  • 1Department of Physiology and Biophysics, University of Southern California, Los Angeles, California 90033, USA.

The Journal of Clinical Investigation
|June 7, 2008
PubMed

Insights

High glucose levels activate a kidney pathway involving GPR91, leading to renin release and potential hypertension in diabetes. This discovery sheds light on metabolic syndrome and kidney disease mechanisms.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetes mellitus is a leading cause of end-stage renal disease.
  • Activation of the renin-angiotensin system (RAS) is a hallmark of early diabetes, linked to hypertension and kidney injury.
  • The precise mechanism of RAS activation in diabetes remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which high glucose levels activate the renin-angiotensin system in the kidney.
  • To identify novel signaling pathways involved in glucose-induced renin release.

Main Methods:

  • Analysis of kidney tissue sections from rats, mice, and rabbits.
  • Investigation of paracrine signaling pathways in the glomerular endothelium.
  • Assessment of intracellular signaling elements including calcium (Ca2+), nitric oxide (NO), and prostaglandin E2 (PGE2).

Main Results:

  • High glucose directly triggers renin release via a paracrine pathway in the kidney.
  • This pathway involves succinate accumulation and activation of the G protein-coupled receptor GPR91 in glomerular endothelial cells.
  • Signal transduction includes endothelial Ca2+, NO production, and PGE2, acting on renin-producing cells.

Conclusions:

  • The identified GPR91 signaling cascade links metabolic disturbances like diabetes to RAS overactivation and hypertension.
  • This pathway may play a role in modulating kidney function and waste product removal through hyperfiltration.
  • Understanding this mechanism offers potential therapeutic targets for diabetic kidney disease and associated hypertension.

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