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Urinary adenosine excretion in type 1 diabetes.
Harindra Rajasekeran1,2, Yuliya Lytvyn1,3, Andrea Bozovic4
1Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
American Journal of Physiology. Renal Physiology
|April 7, 2017
Summary
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) increase urinary adenosine excretion in type 1 diabetes patients. This suggests a potential mechanism for SGLT2i
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is associated with altered renal hemodynamics, including hyperfiltration, potentially mediated by reduced adenosine levels.
- Sodium-glucose cotransporter-2 (SGLT2) activity influences sodium delivery to the macula densa, impacting adenosine generation and renal blood flow.
- The role of urinary adenosine in human diabetic kidney disease and its modulation by SGLT2 inhibitors remains underexplored.
Purpose of the Study:
- To validate a method for quantifying urinary adenosine in humans.
- To investigate the dynamic changes in urinary adenosine levels in response to natriuresis in patients with type 1 diabetes (T1D).
- To explore the effect of the SGLT2 inhibitor (SGLT2i) empagliflozin on urinary adenosine excretion in T1D patients.
Main Methods:
- Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for urine adenosine quantification.
- Measurement of urinary adenosine corrected for creatinine in 40 healthy participants and 40 T1D patients.
- Analysis of urinary adenosine levels in T1D patients under clamped euglycemic and hyperglycemic conditions before and after 8 weeks of SGLT2i therapy.
Main Results:
- The LC-MS/MS method successfully quantified urinary adenosine in both healthy subjects and T1D patients.
- Treatment with empagliflozin led to a significant increase in urinary adenosine excretion during clamped hyperglycemia in T1D patients (0.40 ± 0.11 vs. 0.45 ± 0.12 µmol/mmol Cr, P = 0.005).
- A similar, though not statistically significant, trend of increased urinary adenosine was observed during clamped euglycemia (P = 0.08).
Conclusions:
- SGLT2 inhibitors increase urinary adenosine excretion in type 1 diabetes patients, particularly under hyperglycemic conditions.
- This finding supports the hypothesis that SGLT2i may mitigate glomerular hyperfiltration through increased adenosine-mediated vasodilation.
- Further research is warranted to elucidate the protective role of SGLT2i and its mediation by adenosine in diabetic kidney disease.