Cardiovascular
How might dapagliflozin ease diabetic stiff hearts?
Open access · cc by · source: Europe PMC
In 30 rabbits, dapagliflozin lessened diabetes-related diastolic dysfunction and fibrosis by downregulating SGK1 and ENaC, with matching H9C2 cell results.
How this study connects
Role on claims
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The knockdown reproducing the drug effect is what places SGK1 on the path.
Mechanistic work supplies a pathway the human studies cannot. In diabetic animals and H9C2 cells, dapagliflozin attenuated diastolic dysfunction and reduced fibrosis via SGK1 and ENaC inhibition, with SGK1 knockdown reproducing the drug's effect on ENaC and NHE1.
Evidence for the claim as stated.
Study at a glance
- Design
- Animal / in-vitro — Alloxan-diabetic rabbits randomized to dapagliflozin vs diabetes vs control, plus fibrotic H9C2 SGK1 mechanistic assays
- N
- N=30 · 30 male New Zealand white rabbits, n=10 per control/diabetes/diabetes+dapagliflozin group; plus H9C2 cells
- Population
- Male New Zealand white rabbits with alloxan-induced diabetes and fibrosis-induced H9C2 cardiomyoblasts
- Outcome
- LV diastolic function, myocardial fibrosis, SGK1/ENaC/NHE1 signaling, inflammation, and mitochondrial structure
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Inspect source passages
How might dapagliflozin ease diabetic stiff hearts?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
30 male NZ white rabbits randomized n=10 per group.
A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups ( n = 10/per each group).
Three experimental arms: control, diabetes, diabetes+dapagliflozin.
randomized into control, diabetes, or diabetes+dapagliflozin groups ( n = 10/per each group).
Key findings
Diabetes+dapagliflozin attenuated diastolic dysfunction vs diabetes alone. Fibrosis fell via SGK1 and ENaC inhibition in tissue and H9C2 cells. Dapagliflozin was anti-inflammatory and eased mitochondrial disruption; siSGK1 reduced ENaC and NHE1 similarly to the drug.
Methodology
Randomized 30 male NZ white rabbits to control, diabetes (IV alloxan), or diabetes+dapagliflozin (n=10 each); assessed echo, histology, and molecules, and probed SGK1 with siRNA in fibrotic H9C2 cells.
Limitations
Alloxan-rabbit and H9C2 data do not prove SGK1 is the only human mechanism or replace large SGLT2i outcome trials.
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