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Cocaine- and Amphetamine-regulated Transcript (CART) Protects Beta Cells against Glucotoxicity and Increases Cell Proliferation

Sathanoori, Ramasri LU ; Olde, Björn LU ; Erlinge, David LU ; Göransson, Olga LU and Wierup, Nils LU (2013) In Journal of Biological Chemistry 288(5). p.3208-3218
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
288
issue
5
pages
3208 - 3218
publisher
ASBMB
external identifiers
  • wos:000314397900028
  • pmid:23250745
  • scopus:84873320832
  • pmid:23250745
ISSN
1083-351X
DOI
10.1074/jbc.M112.437145
language
English
LU publication?
yes
id
dbd4c900-edc5-4b83-9e22-b8eb8e0ba37f (old id 3347074)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23250745?dopt=Abstract
date added to LUP
2016-04-01 10:40:00
date last changed
2020-01-12 04:59:12
@article{dbd4c900-edc5-4b83-9e22-b8eb8e0ba37f,
  abstract     = {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.},
  author       = {Sathanoori, Ramasri and Olde, Björn and Erlinge, David and Göransson, Olga and Wierup, Nils},
  issn         = {1083-351X},
  language     = {eng},
  number       = {5},
  pages        = {3208--3218},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Cocaine- and Amphetamine-regulated Transcript (CART) Protects Beta Cells against Glucotoxicity and Increases Cell Proliferation},
  url          = {http://dx.doi.org/10.1074/jbc.M112.437145},
  doi          = {10.1074/jbc.M112.437145},
  volume       = {288},
  year         = {2013},
}