Hatanaka Ryoko, Taguchi Akihiko, Nagao Yuko, Yorimoto Kaito, Takesato Akari, Masuda Konosuke, Ono Takao, Samukawa Yoshishige, Tanizawa Yukio, Ohta Yasuharu
Division of Endocrinology, Metabolism, Hematological Science and Therapeutics, Yamaguchi University, Graduate School of Medicine, 1-1-1, Minami Kogushi, Ube, 755-8505, Japan.
Quality Assurance Headquarters, Taisho Pharmaceutical Co., Ltd., 3-24-1, Takada, Toshima-ku, Tokyo, 170-8633, Japan.
Heliyon. 2024 Aug 8;10(16):e35978. doi: 10.1016/j.heliyon.2024.e35978. eCollection 2024 Aug 30.
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.
据报道，类黄酮家族成员紫苏亭在长期给药后可改善葡萄糖代谢，但其潜在机制的细节尚不清楚。我们发现，在小鼠胰岛和MIN6细胞的高葡萄糖浓度下，紫苏亭可使胰岛素分泌增加约一倍。当给小鼠口服紫苏亭时，早期胰岛素分泌增加，葡萄糖负荷后30分钟血糖水平降低30%。胰岛素耐量试验也表明紫苏亭可提高全身胰岛素敏感性。此外，我们观察到紫苏亭可提高胰岛细胞内cAMP水平。磷酸二酯酶（PDE）活性测定显示紫苏亭可抑制PDE活性，计算机模拟预测PDE与紫苏亭之间具有高结合亲和力。这些发现表明，紫苏亭通过抑制PDE导致细胞内cAMP增加，从而增强胰岛素分泌和胰岛素敏感性。这些见解可能有助于理解紫苏亭和其他异黄酮调节葡萄糖代谢的潜在机制。
