Document Detail


Ion channels underlying stimulus-exocytosis coupling and its cell-to-cell heterogeneity in beta-cells of transplantable porcine islets of Langerhans.
MedLine Citation:
PMID:  19242122     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Given the growing interest in porcine islets as model tissue for studying the pathogenesis of human diabetes mellitus and its treatment by transplantation, we investigated stimulus-exocytosis coupling in single porcine beta-cells using patch clamp electrophysiology, Ca2+ imaging, capacitance tracking and amperometry. We establish that porcine beta-cells display several features prominently seen in beta-cells from human islets of Langerhans. These include: (i) wide heterogeneity of electrical responsiveness to glucose; (ii) dependence of action potential activity on voltage-dependent Na(+) as well as high voltage activated Ca2+ current; (iii) heterogeneity of time course of depolarization-evoked insulin granule exocytosis; and (iv) the dependence of vigorous single cell electrical activity and insulin granule exocytosis on the presence of agents that enhance cytosolic cAMP concentration. These findings promote the usefulness of porcine beta-cells as a model for studying beta-cell function in large mammals, including humans, as well as an appropriate source of tissue for xenotransplantation.
Authors:
Amelia M Silva; Adam S Dickey; David W Barnett; Stanley Misler
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-16
Journal Detail:
Title:  Channels (Austin, Tex.)     Volume:  3     ISSN:  1933-6969     ISO Abbreviation:  Channels (Austin)     Publication Date:    2009 Mar-Apr
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-09-01     Revised Date:  2010-01-15    
Medline Journal Info:
Nlm Unique ID:  101321614     Medline TA:  Channels (Austin)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-100     Citation Subset:  IM    
Affiliation:
Departments of Internal Medicine and Cell Biology/Physiology, Washington University Medical Center, Saint Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Animals
Calcium / metabolism
Electrophysiology
Exocytosis*
Glucose / pharmacology
Humans
Insulin-Secreting Cells / physiology*
Ion Channels / metabolism*
Islets of Langerhans / cytology,  physiology
Islets of Langerhans Transplantation*
Models, Animal
Sodium / metabolism
Swine
Grant Support
ID/Acronym/Agency:
4R01-DK37380/DK/NIDDK NIH HHS; 5T32 GM07281/GM/NIGMS NIH HHS; R0I-DK20579/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Ion Channels; 50-99-7/Glucose; 7440-23-5/Sodium; 7440-70-2/Calcium

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


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