Pyruvate dehydrogenase kinase 4 inhibition or deletion in alpha-cells enhances glucagon secretion at low glucose in mouse and human islets and improves glucose tolerance in diet-induced obese male mice

Butaye, François;Gilon, Patrick
(2025) 61st EASD Annual Meeting of the European Association for the Study of Diabetes — Location: (Austria) Vienna (15.September.2025)

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BACKGROUND AND AIMS: The mechanisms of control of glucagon secretion are still largely unknown. In particular, it is unclear why glucose inhibits glucagon secretion while fatty acids stimulate it. These divergent effects may result from an intrinsic property of α-cells, potentially linked to their high expression of pyruvate dehydrogenase kinase 4 (PDK4). PDK1-4 phosphorylate and inactivate pyruvate dehydrogenase, which converts pyruvate into acetyl-CoA. This study aims to investigate the role of PDK4 in α-cells in the control of glucagon secretion and glucose homeostasis. [...]
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Butaye, F., & Gilon, P. (2025). Pyruvate dehydrogenase kinase 4 inhibition or deletion in alpha-cells enhances glucagon secretion at low glucose in mouse and human islets and improves glucose tolerance in diet-induced obese male mice. Diabetologia : clinical and experimental diabetes and metabolism, 68(Suppl 1), S140. https://hdl.handle.net/2078.5/259485 (Original work published 2025)