Diabetes is an increasingly common cause of kidney failure in developed countries. It is thought that activation of a hormone system known as the renin-angiotensin system (RAS) early in the course of diabetes has an important role in the development of kidney disease.
New data, generated using mice, rats, and rabbits, by Jαnos Peti-Peterdi and colleagues, at the University of Southern California, Los Angeles, have provided new insight into the mechanisms by which the RAS might be activated in individuals with diabetes.
Individuals with diabetes have increased levels of glucose in their blood and other bodily fluids. In the study, in vitro exposure of rat, mouse, and rabbit kidney to high levels of glucose triggered cells in the kidney to release renin and this was associated with accumulation of a molecule known as succinate.
Consistent with this having a role in human diabetes, diabetic mice had higher levels of succinate in their kidney than did nondiabetic mice.
Furthermore, diabetic mice lacking the protein GPR91, which recognizes succinate, had less renin in their kidney that did diabetic mice expressing GPR91. The authors therefore suggest that GPR91 might be a new therapeutic target to prevent the kidney failure that can be a complication of diabetes.
- Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. Journal of Clinical Investigation, June 5, 2008
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