Abstract：
:Defects in insulin secretion play a central role in the pathogenesis of type 2 diabetes, yet the mechanisms driving beta-cell dysfunction remain poorly understood, and therapies to preserve glucose-dependent insulin release are inadequate. We report a luminescent insulin secretion assay that enables large-scale investigations of beta-cell function, created by inserting Gaussia luciferase into the C-peptide portion of proinsulin. Beta-cell lines expressing this construct cosecrete luciferase and insulin in close correlation, under both standard conditions or when stressed by cytokines, fatty acids, or ER toxins. We adapted the reporter for high-throughput assays and performed a 1,600-compound pilot screen, which identified several classes of drugs inhibiting secretion, as well as glucose-potentiated secretagogues that were confirmed to have activity in primary human islets. Requiring 40-fold less time and expense than the traditional ELISA, this assay may accelerate the identification of pathways governing insulin secretion and compounds that safely augment beta-cell function in diabetes.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Burns SM,Vetere A,Walpita D,Dančík V,Khodier C,Perez J,Clemons PA,Wagner BK,Altshuler Ddoi
10.1016/j.cmet.2014.12.010subject
Has Abstractpub_date
2015-01-06 00:00:00pages
126-37issue
1eissn
1550-4131issn
1932-7420pii
S1550-4131(14)00561-0journal_volume
21pub_type
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