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

Bioorg Med Chem Lett. 2021 Jul 1:43:128096. doi: 10.1016/j.bmcl.2021.128096. Epub 2021 May 10.

Abstract

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.

Keywords: AKT; Insulin; Morus alba; PDX-1; PI3K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Glucose / antagonists & inhibitors*
  • Glucose / pharmacology
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Insulin Secretion / drug effects*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Molecular Structure
  • Rats
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds
  • Hypoglycemic Agents
  • Glucose