Identification of bioactive compounds from mulberry enhancing glucose-stimulated insulin secretion

• Published in: Bioorganic & medicinal chemistry letters Vol. 43; p. 128096
• Main Authors: Lee, Dahae, Kim, Ki Hyun, Jang, Tae Su, Kang, Ki Sung
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2021
• Subjects: AKT; Insulin; Morus alba; PDX-1; PI3K; AKT; PI3K; Morus alba; Insulin; PDX-1
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.128096

[Display omitted] Previously, we isolated six heterocyclic compounds (1–6) from the fruits of mulberry trees (Morus alba L.) and determined that loliolide affords rat pancreatic islet β-cell (INS-1) protection against streptozotocin‑induced cytotoxicity. In the present study, we further investigated the effect of the six heterocyclic compounds (1–6) on glucose-stimulated insulin secretion (GSIS) in INS-1 cells. Among them, (R)‑5‑hydroxypyrrolidin‑2‑one(1) and indole (6) increased GSIS without inducing cytotoxicity. Additionally, compounds 1 and 6 enhanced the phosphorylation of total insulin receptor substrate-2, phosphatidylinositol 3-kinase, and Akt, and activated pancreatic and duodenal homeobox-1, which play a crucial role in β-cell functions related to insulin secretion. Collectively, these findings indicate that (R)‑5‑hydroxypyrrolidin‑2‑one(1) and indole (6), isolated from M. alba fruits, may be beneficial in managing type 2 diabetes.