Cocaine- and Amphetamine-regulated Transcript (CART) Protects Beta Cells against Glucotoxicity and Increases Cell Proliferation
Author
Summary, in English
Cocaine and amphetamine-regulated transcript (CART) is an islet peptide that promotes glucose stimulated insulin secretion in beta cells via cAMP/PKA-dependent pathways. In addition, CART is a regulator of neuronal survival. In this study, we examined the effect of exogenous CART 55-102 on beta cell viability and dissected its signaling mechanisms. Evaluation of DNA fragmentation and chromatin condensation revealed that CART 55-102 reduced glucotoxicity-induced apoptosis in both INS-1 (832/13) cells and isolated rat islets. Furthermore, glucotoxicity in INS-1 (832/13) cells caused a 50% reduction of endogenous CART protein. In addition, CART increased proliferation in INS-1 (832/13) cells; an effect that was blocked by PKA, PKB, and MEK1 inhibitors. Further, in INS-1 (832/13) cells and isolated rat islets, CART induced phosphorylation of CREB, IRS-2, PKB, FoxO1, p44/42 MAPK, and p90RSK; all key mediators of cell survival and proliferation. Thus, we demonstrate that CART 55-102 protects beta cells against glucotoxicity and promotes proliferation. Taken together our data points to the potential use of CART in therapeutic interventions targeted at enhancing functional beta cell mass and long-term insulin secretion in T2D.
Publishing year
2013
Language
English
Pages
3208-3218
Publication/Series
Journal of Biological Chemistry
Volume
288
Issue
5
Links
Document type
Journal article
Publisher
American Society for Biochemistry and Molecular Biology
Topic
- Endocrinology and Diabetes
Status
Published
Research group
- Neuroendocrine Cell Biology
ISBN/ISSN/Other
- ISSN: 1083-351X