Biochemical reassessment of the activation of PANK1 by SGLT2 inhibitors

Empagliflozin and dapagliflozin did not stimulate purified recombinant human PANK1 activity in either basal or acetyl-CoA feedback conditions, unlike PZ-2891.

• Why it matters: The molecular target behind SGLT2 inhibitor cardiovascular benefits is uncertain, and a prior report proposed direct PANK1 activation as the mechanism.
• What they did: The claim was reassessed with purified recombinant human PANK1 using malachite green and ADP-Glo assays, including tests under basal conditions and acetyl-CoA feedback inhibition.
• The result: ADP-Glo showed no PANK1 activation by empagliflozin or dapagliflozin, whereas PZ-2891 increased activity, challenging a PANK1-dependent cardioprotection mechanism.

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