How might dapagliflozin ease diabetic stiff hearts?
In 30 rabbits, dapagliflozin lessened diabetes-related diastolic dysfunction and fibrosis by downregulating SGK1 and ENaC, with matching H9C2 cell results.
Source
Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling
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).
What they did
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.
What they found
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.
The limits
What it doesn't show
Alloxan-rabbit and H9C2 data do not prove SGK1 is the only human mechanism or replace large SGLT2i outcome trials.
Key terms
- Dapagliflozin
- SGLT2 inhibitor studied here for diabetic cardiac effects.
- SGK1
- Serum/glucocorticoid-regulated kinase 1 implicated in fibrosis signaling.
- ENaC
- Epithelial sodium channel downstream of SGK1 in this model.
- Diastolic dysfunction
- Impaired left-ventricular relaxation/filling.
- H9C2
- Rat cardiomyoblast line used for mechanistic fibrosis assays.
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Rabbits per group:
Common questions
Animal sample?
30 rabbits, 10 per control/diabetes/diabetes+dapagliflozin.
How was diabetes induced?
Intravenous alloxan.
Key signaling axis?
SGK1 and ENaC (and NHE1).
Functional benefit?
Attenuated LV diastolic dysfunction and cardiac fibrosis.
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