AI Article Synopsis
- The second messenger cAMP boosts insulin secretion from pancreatic β-cells, but its specific targets are not well-defined.
- Researchers created cAMP analogues that selectively activate Epac2, showing significantly higher potency than cAMP itself.
- One designed agonist, S-220, successfully increases insulin secretion in human pancreatic cells, suggesting a potential new strategy for diabetes treatment.
Article Abstract
The second messenger cAMP is known to augment glucose-induced insulin secretion. However, its downstream targets in pancreatic β-cells have not been unequivocally determined. Therefore, we designed cAMP analogues by a structure-guided approach that act as Epac2-selective agonists both in vitro and in vivo. These analogues activate Epac2 about two orders of magnitude more potently than cAMP. The high potency arises from increased affinity as well as increased maximal activation. Crystallographic studies demonstrate that this is due to unique interactions. At least one of the Epac2-specific agonists, Sp-8-BnT-cAMPS (S-220), enhances glucose-induced insulin secretion in human pancreatic cells. Selective targeting of Epac2 is thus proven possible and may be an option in diabetes treatment.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300089 | PMC |
| http://dx.doi.org/10.1371/journal.pbio.1002038 | DOI Listing |
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