Abstract:
:Cyclin-dependent kinases (CDKs) contribute to vital cellular processes including cell cycle regulation. Loss of CDKs is associated with impaired insulin secretion and β cell survival; however, the function of CDK8 in β cells remains elusive. Here, we report that genetic ablation of Cdk8 improves glucose tolerance by increasing insulin secretion. We identify OSBPL3 as a CDK8-dependent phosphoprotein, which acts as a negative regulator of insulin secretion in response to glucose. We also show that embryonic gene silencing of neuropeptide Y in β cells is compromised in Cdk8-null mice, leading to continued expression into adulthood. Cdk8 ablation in β cells aggravates apoptosis and induces de novo expression of neuropeptides upon oxidative stress. Moreover, pancreatic islets exposed to stress display augmented apoptosis in the presence of these same neuropeptides. Our results reveal critical roles for CDK8 in β cell function and survival during metabolic stress that are in part mediated through de novo expression of neuropeptides.
journal_name
Cell Repjournal_title
Cell reportsauthors
Xue J,Scotti E,Stoffel Mdoi
10.1016/j.celrep.2019.08.025subject
Has Abstractpub_date
2019-09-10 00:00:00pages
2892-2904.e7issue
11issn
2211-1247pii
S2211-1247(19)31059-9journal_volume
28pub_type
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