Trapa Bispinosa Roxb. Inhibits the Insulin-Dependent AKT/WNK1 Pathway to Induce Autophagy in Mice with Type 2 Diabetes

Takahiro Suzuki; Takehito Sato; Kaori Masuhara; Mizuki Tokusanai; Hisako Akatsuka; Tomohiro Kashikawa; Yasuyuki Suzuki

doi:10.2147/DMSO.S430132

Trapa Bispinosa Roxb. Inhibits the Insulin-Dependent AKT/WNK1 Pathway to Induce Autophagy in Mice with Type 2 Diabetes

Diabetes Metab Syndr Obes. 2023 Oct 5:16:3095-3104. doi: 10.2147/DMSO.S430132. eCollection 2023.

Authors

Takahiro Suzuki¹, Takehito Sato², Kaori Masuhara², Mizuki Tokusanai², Hisako Akatsuka², Tomohiro Kashikawa², Yasuyuki Suzuki¹

Affiliations

¹ Department of Ophthalmology, Tokai University School of Medicine, Kanagawa, Japan.
² Department of Immunology, Tokai University School of Medicine, Kanagawa, Japan.

Abstract

Purpose: To elucidate the antiglycation activity of Trapa bispinosa Roxb. extract (TBE) and the related mechanism using a mouse model with type 2 diabetes.

Materials and methods: We prepared control mice by giving them a normal diet, leptin-deficient ob/ob mouse (ob/ob mice) with a normal diet (normal ob/ob mice), and ob/ob mice with a diet containing TBE (TBE ob/ob mice). The effect of TBE on diabetic retina was evaluated by immunohistochemical staining and quantitative real-time polymerase chain reaction (qPCR) analysis.

Results: In both groups with ob/ob mice, body weight and hyperglycemia levels increased over time. Immunohistochemical staining analysis revealed that glial fibrillary acidic protein (GFAP) and advanced glycation end products (AGEs) expression levels were higher in normal ob/ob mice than in control mice, and lower in the TBE ob/ob mice than in normal ob/ob mice. Light chain-3 (LC-3) expression levels reduced in normal ob/ob mice compared to the control mice, but increased in TBE ob/ob mice compared to normal ob/ob mice. In the qPCR analysis, LC-3 expression levels were significantly lower in normal ob/ob mice compared to control mice, and significantly higher in TBE ob/ob mice compared to normal ob/ob mice. Conversely, AKT1 and with-no-lysine kinases 1 (WNK1) expression levels were significantly higher in normal ob/ob mice compared to control mice, and significantly lower in TBE ob/ob mice than in normal ob/ob mice.

Conclusion: In type 2 diabetes, it was suggested that TBE inhibits the insulin-dependent AKT/WNK1 pathway to induce autophagy, and thereby might promote anti-glycation and reduce retinal damage.

Keywords: Trapa bispinosa Roxb. extract; advanced glycation end products; autophagy; diabetic retinopathy; insulin-dependent AKT/WNK1 pathway; type 2 diabetes.