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


CONCLUSIONS
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.
Zhang
Yu
Y
Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Li
Yan
Y
Guo
Yue-wei
YW
Jiang
Hua-liang
HL
Shen
Xu
X
D041721:3T3-L1 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D047088:Dysidea / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D011809:Quinones; D012717:Sesquiterpenes; C433902:dysidine; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; D005947:Glucose