The flavonoid Sudachitin regulates glucose metabolism via PDE inhibition.

Sudachitin, a member of the flavonoid family, reportedly improves glucose metabolism after long-term administration, but details of the underlying mechanisms are unknown. We found that Sudachitin approximately doubles insulin secretion under high glucose concentrations in mouse pancreatic islets and MIN6 cells. When Sudachitin was orally administered to mice, early-phase insulin secretion was increased and a 30 % reduction in blood glucose levels was demonstrated 30 min after glucose loading. Insulin tolerance tests also showed Sudachitin to increase systemic insulin sensitivity. Additionally, we observed that Sudachitin raised intracellular cAMP levels in pancreatic islets. Phosphodiesterase (PDE) activity assays revealed Sudachitin to inhibit PDE activity and computer simulations predicted a high binding affinity between PDEs and Sudachitin. These findings suggest that Sudachitin enhances both insulin secretion and insulin sensitivity via an increase in intracellular cAMP resulting from PDE inhibition. These insights may facilitate understanding the mechanisms underlying the regulation of glucose metabolism by Sudachitin and other isoflavones.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akihiko Taguchi reports financial support was provided by Taisho Pharmaceutical Co., Ltd. Akihiko Taguchi reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. Akihiko Taguchi reports financial support was provided by 10.13039/501100011907Mishima Kaiun Memorial Foundation. Yasuharu Ohta reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. Yukio Tanizawa reports financial support was provided by the 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Authors.)