A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTPases

Abstract

Aim:The sesquiterpene hydroquinones/quinones belong to one class of marine sponge metabolites, and they have received considerable attention due to their varied biological activities, including anti-tumor, anti-HIV, and anti-inflammatory action. In order to probe the potential anti-diabetic effect of the sesquiterpene hydroquinones/quinones, the effect of dysidine on the insulin pathway was studied. Methods: The promotion of glucose uptake by dysidine was studied in differentiated 3T3-L1 cells. The increase in membrane-located GLUT4 by dysidine was studied in CHO-K1/GLUT4 and 3T3-L1 cells by immuno-staining. The activation of the insulin signaling pathway by dysidine was probed by Western blotting. The inhibition of PTPases by dysidine was detected in vitro. Results: Dysidine, found in the Hainan sponge Dysidea villosa in the Chinese South Sea, effectively activated the insulin signaling pathway, greatly promoted glucose uptake in 3T3-L1 cells, and showed strong insulin-sensitizing activities. The potential targets of action for dysidine were probed, and the results indicated that dysidine exhibited its cellular effects through activation of the insulin pathway, possibly through the inhibition of protein tyrosine phosphatases, with more specific inhibition against protein tyrosine phosphatase 1B (PTP1B). Conclusion: Our findings are expected to expand understanding of the biological activities of sesquiterpene hydroquinones/quinones, and they show that dysidine could be a potential lead compound in the development of an alternative adjuvant in insulin therapy.

Marine Organisms with Anti-Diabetes Properties

“…Inhibitory effects on the enzyme PTP1B have been reported for a polybromodiphenyl ether from the Indonesian marine sponge Lamellodysidea herbacea [75] and for the terpene Dysidine, from the sponge Dysidea sp. [23,76], that has recently entered pre-clinical trials for the treatment of type-2 diabetes [23]. Dysidine was found for the first time in a sponge at Lahdu (Santo) in Vanuatu in June 1996, identified as sponge Dysidea sp.…”

Bioactive natural products from Chinese marine flora and fauna

“…The chemical study on another Dysidea sp led to the discovery of a new sesquiterpene quinone (42), along with a known related analog dysidine (43) [31] ( Figure 7). A bioassay showed that dysidine (43) µmol/L, respectively [32] . Three unprecedented diastereoisomeric dimers, cis-dimers A (44) and B (45) and trans-dimer C (46), representing bisbisabolene skeletons, and their potential precursor dehydrotheonelline (47) have been isolated from the South China Sea sponges Axinyssa variabilis and Lipastrotethya ana [33] ( Figure 7).…”

Chapter 6. Recent Advances in PTP1B Inhibitor Development for the Treatment of Type 2 Diabetes and Obesity

“…145 Subsequent studies showed that it effectively activated the insulin signaling pathway and greatly promoted glucose uptake in 3T3-L1 cells. 146 From the roots of Suussurea lappa, Hu obtained one new lignan glycoside along with 20 known compounds, which were tested against PTP1B. 147 Rhein-8-O-b-Dglucopyrariosidc (113) showed the best activity with an IC 50 of 11.5 mM.…”