Linked Life Data

11272144

Source:http://linkedlifedata.com/resource/pubmed/id/11272144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-22
pubmed:databankReference
pubmed:abstractText
Hyperinsulinism of infancy (HI) is a congenital defect in the regulated release of insulin from pancreatic beta-cells. Here we describe stimulus-secretion coupling mechanisms in beta-cells and intact islets of Langerhans isolated from three patients with a novel SUR1 gene defect. 2154+3 A to G SUR1 (GenBank accession number L78207) is the first report of familial HI among nonconsanguineous Caucasians identified in the U.K. Using patch-clamp methodologies, we have shown that this mutation is associated with both a decrease in the number of operational ATP-sensitive K+ channels (KATP channels) in beta-cells and impaired ADP-dependent regulation. There were no apparent defects in the regulation of Ca2+- and voltage-gated K+ channels or delayed rectifier K+ channels. Intact HI beta-cells were spontaneously electrically active and generating Ca2+ action currents that were largely insensitive to diazoxide and somatostatin. As a consequence, when intact HI islets were challenged with glucose and tolbutamide, there was no rise in intracellular free calcium ion concentration ([Ca2+]i) over basal values. Capacitance measurements used to monitor exocytosis in control and HI beta-cells revealed that there were no defects in Ca2+-dependent exocytotic events. Finally, insulin release studies documented that whereas tolbutamide failed to cause insulin secretion as a consequence of impaired [Ca2+]i signaling, glucose readily promoted insulin release. Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-39
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11272144-ATP-Binding Cassette Transporters, pubmed-meshheading:11272144-Adenosine Diphosphate, pubmed-meshheading:11272144-Adenosine Triphosphate, pubmed-meshheading:11272144-Calcium, pubmed-meshheading:11272144-Calcium Signaling, pubmed-meshheading:11272144-Cytosol, pubmed-meshheading:11272144-Exocytosis, pubmed-meshheading:11272144-Genotype, pubmed-meshheading:11272144-Humans, pubmed-meshheading:11272144-Hyperinsulinism, pubmed-meshheading:11272144-Infant, Newborn, pubmed-meshheading:11272144-Insulin, pubmed-meshheading:11272144-Islets of Langerhans, pubmed-meshheading:11272144-Molecular Sequence Data, pubmed-meshheading:11272144-Mutation, pubmed-meshheading:11272144-Patch-Clamp Techniques, pubmed-meshheading:11272144-Potassium Channels, pubmed-meshheading:11272144-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:11272144-Receptors, Drug
pubmed:year
2001
pubmed:articleTitle
Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways.
pubmed:affiliation
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't