Dataset Information
Antagonistic interaction between Nodal and insulin modulates pancreatic ?-cell proliferation and survival.
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ABSTRACT: Background
Insulin signaling pathway in ?-cell is essential to promote ?-cells proliferation and survival, while Nodal-ALK7-Smad3 signaling involves ?-cells apoptosis. We attempted to address inter-relationship between Nodal and insulin in modulating ?-cell proliferation and apoptosis.Methods
Using INS-1 ?-cells and isolated rat islets, we examined the effects of Nodal, insulin, or the two combined on ?-cell proliferation and/or apoptosis.Results
The ?-cells under high-glucose or palmitate conditions showed significant up-regulation of Nodal expression and activation of its downstream signaling pathway resulted in increased cleaved caspase-3. Insulin treatment led to significantly attenuated Nodal-induced cell apoptotic pathway. Similar results were found in directly Nodal-treated ?-cell that insulin could partially block Nodal-induced up-regulation of ALK7-Smad3-caspase-3 signaling pathways with significantly attenuated ?-cell apoptosis. Interestingly, we found that insulin-induced Akt activation and downstream molecules including GSK-3?, ?-catenin and ERK1/2 was significantly attenuated by the co-treatment with Nodal, resulted in decreased cell proliferation. Furthermore, Nodal decreased glucose-evoked calcium influx and played a negative role during glucose-stimulated insulin secretion in the ?-cells. Immunocytochemistry studies showed that Nodal treatment translocated Smad3 from cytosol mostly to the nucleus; however, co-treatment with insulin significantly decreased Smad3 nuclear localization. Co-immunoprecipitation experiments showed a directly interaction between Smad3 and Akt, and this interaction was enhanced by co-treatment with insulin.Conclusions
Our data suggest that the antagonistic interaction between Nodal and insulin has a role in the regulation of ?-cell mass and secretion.
SUBMITTER: Li J
PROVIDER: S-EPMC6225724 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Antagonistic interaction between Nodal and insulin modulates pancreatic β-cell proliferation and survival.
Cell communication and signaling : CCS 20181108 1
<h4>Background</h4>Insulin signaling pathway in β-cell is essential to promote β-cells proliferation and survival, while Nodal-ALK7-Smad3 signaling involves β-cells apoptosis. We attempted to address inter-relationship between Nodal and insulin in modulating β-cell proliferation and apoptosis.<h4>Methods</h4>Using INS-1 β-cells and isolated rat islets, we examined the effects of Nodal, insulin, or the two combined on β-cell proliferation and/or apoptosis.<h4>Results</h4>The β-cells under high-gl ...[more]