2,3-Dihydrosorbicillin and chrysopanol stimulate insulin secretion in INS-1 cells.

Pancreatic β-cell function and insulin secretion are important in antidiabetic drug development. In an effort to discover small molecules to regulate insulin secretion, an endophytic fungus, Penicillium sp. SSP-1CLG, was selected for chemical investigation. Large scale cultures of the strain followed by extraction and chromatographic analysis led to the isolation of 10 anthraquinone and alkaloid-type compounds. The isolated compounds were identified by comprehensive analysis of NMR, MS, and ECD data. The effect of compounds 1-10 on insulin secretion in INS-1 cells was investigated. 2,3-Dihydrosorbicillin (1), chrysophanol (2), and glandicolin B (10) at non-cytotoxic concentrations resulted in an increase of glucose-stimulated insulin secretion (GSIS) in rat INS-1 pancreatic β-cells. Furthermore, we investigated the signaling pathway involved in 2,3-dihydrosorbicillin (1) and chrysophanol (2) action in the activation of peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox-1 (PDX-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt. Treatment of INS-1 cells with 2,3-dihydrosorbicillin (1) and chrysophanol (2) increased the expression of these proteins. Our findings indicate that 2,3-dihydrosorbicillin and chrysophanol may play roles in the regulation of insulin secretion in pancreatic β-cells, at least in part, by targeting PPARγ and PDX-1 via the IRS-2/PI3K/Akt signaling pathway. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Dahae Lee, Jaekyung Kim, Sungyoul Choi, Jinwon Choi, Jin Woo Lee, Ki Sung Kang, Sang Hee Shim. 2,3-Dihydrosorbicillin and chrysopanol stimulate insulin secretion in INS-1 cells. Bioorganic & medicinal chemistry letters. 2023 Mar 01;83:129186

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PMID: 36781148

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