Document Detail


Autocrine insulin action activates Akt and increases survival of isolated human islets.
MedLine Citation:
PMID:  17053882     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a critical role in promoting the survival of pancreatic beta cells. Akt becomes activated in isolated human islets following overnight culture despite significant levels of cell death. The aim of the current study was to identify the cause of the observed increase in Akt phosphorylation in isolated islets. We hypothesised that a factor secreted by the islets in culture was acting in an autocrine manner to activate Akt. METHODS: In order to identify the stimulus of the PI3K/Akt pathway in culture, we examined the effects of different culture conditions on Akt phosphorylation and islet survival during the immediate post-isolation period. RESULTS: We demonstrated that islet-conditioned medium induced Akt phosphorylation in freshly isolated human islets, whereas frequent medium replacement decreased Akt phosphorylation. Following overnight culture, islet-conditioned medium contained significantly elevated levels of insulin, indicating that insulin may be responsible for the observed increase in Akt phosphorylation. Indeed, treatment with an anti-insulin antibody or with inhibitors of insulin receptor/IGF receptor 1 kinase activity suppressed Akt phosphorylation, leading to decreased islet survival. In addition, dispersion of islets into single cells also suppressed Akt phosphorylation and induced islet cell death, indicating that islet integrity is also required for maximal Akt phosphorylation. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that insulin acts in an autocrine manner to activate Akt and mediate the survival of isolated human islets. These findings provide new information on how culturing islets prior to transplantation may be beneficial to their survival by allowing for autocrine activation of the pro-survival Akt pathway.
Authors:
R Aikin; S Hanley; D Maysinger; M Lipsett; M Castellarin; S Paraskevas; L Rosenberg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  Diabetologia     Volume:  49     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-10     Completed Date:  2007-09-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2900-9     Citation Subset:  IM    
Affiliation:
Department of Surgery, McGill University, Montreal, QC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Cadaver
Cell Survival
Cells, Cultured
Culture Media, Conditioned
Enzyme Activation
Humans
Insulin / pharmacology*
Islets of Langerhans / cytology*,  drug effects
Kinetics
Middle Aged
Mitochondria / drug effects,  metabolism
Organ Size
Pancreas / anatomy & histology
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism*
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 11061-68-0/Insulin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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