| Coupling of metabolic, second messenger pathways and insulin granule dynamics in pancreatic beta-cells: A computational analysis. | |
| | |
MedLine Citation:
|
PMID: 21920379 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Insulin secretory responses to nutrient stimuli and hormonal modulators in pancreatic beta-cells are controlled by a variety of secondary messengers. We have analyzed numerous mechanisms responsible for regulated exocytosis in these cells and present an integrated mathematical model of cytosolic Ca(2+), cAMP and granule dynamics. The insulin-containing granules in the beta-cell were divided into four classes: a large "reserve" granule pool, a smaller pool of the morphologically docked granules that is chemically 'primed' for release or the "readily releasable pool", and a pool of "restless newcomer granules" that undergoes preferential exocytosis. The model incorporates glucose and other aspects of metabolism, the cAMP amplifying pathway, insulin granule dynamics and the exocyst concept for granule binding. The values of most of the model parameters were inferred from available experimental data. The model can generate both the fast first phase and slow biphasic insulin secretion found experimentally in response to a step increase of membrane potential or of glucose. The numerical simulations have also reproduced a variety of experimental conditions, such as periodic stimulation by high K(+) and the potentiation induced in islets by pre-incubation with cAMP pathway activators. The explicit incorporation of Ca(2+) channels, Ca(2+) and cAMP dynamics allows the model to be further connected to current models for calcium and metabolic dynamics and provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. The model may be important in the identification of pharmacological targets for improving insulin secretion in type 2 diabetes. |
| | |
Authors:
|
Leonid E Fridlyand; Louis H Philipson |
Related Documents
:
|
6504859 - Decidual changes in the endometrium and morphological adaptation of the associated supp... 16835399 - Folate status modulates the induction of hepatic glycine n-methyltransferase and homocy... 16310809 - General administration of cyclohexenonic long-chain fatty alcohol ameliorates hyperreac... 12860309 - Hypoglycaemic effect of water extracts of aegle marmelos fruits in streptozotocin diabe... 17889469 - Assessment of antidiabetic potential of cynodon dactylon extract in streptozotocin diab... 8090839 - Comparison of computerized cystometry/micturition and contractile responses of the diab... 11755479 - Screening and follow-up of diabetic retinopathy using a new mosaic 9-field fundus photo... 10818509 - Inherent abnormalities in energy metabolism in alzheimer disease. interaction with cere... 10871199 - Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin acti... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-9-8 |
Journal Detail:
|
Title: Progress in biophysics and molecular biology Volume: - ISSN: 1873-1732 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-9-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0401233 Medline TA: Prog Biophys Mol Biol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
|
Department of Medicine, The Kovler Diabetes Center, The University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics, The Kovler Diabetes Center, The University of Chicago, Chicago, IL 60637, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transfer profile of intramuscularly administered tetrodotoxin to artificial hybrid specimens of puff...
Next Document: Neurocognitive development in preterm infants: Insights from different approaches.