Linked Life Data

15166124

Source:http://linkedlifedata.com/resource/pubmed/id/15166124

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-8-23
pubmed:abstractText
The ATP-sensitive K+ (KATP) channel, composed of Kir6.2 and sulfonylurea receptor (SUR1), in pancreatic beta-cells is believed to serve as a metabolic sensor regulating insulin secretion according to glucose levels. Thus, genetic disruption of Kir6.2 expression may impair KATP channel function in glucose sensing and insulin secretion. Here we show evidence obtained from functional genetic assays supporting this hypothesis. To avoid adaptive cellular mechanisms in transgenic preparations, we designed a hammerhead ribozyme that specifically targeted the Kir6.2 mRNA at serine 78. The Kir6.2-ribozyme was constructed in an adenoviral vector and expressed in insulin-secreting RINm5F cells. Both RT-PCR and Northern blot analyses showed that Kir6.2 transcripts were significantly reduced with a Kir6.2-ribozyme treatment. Whole-cell patch-clamp studies indicated that the Kir6.2-ribozyme treatment lowered KATP channel density by 66%. In response to higher glucose challenge, insulin release from the RINm5F cells dropped by approximately 20% in a transfection dose of 0.7 multiplicity of infection, and by 30-40% in a dose of 2.7 multiplicity of infection. These results therefore indicate that KATP channels play an important role in glucose sensing and insulin secretion, and ribozyme Kir6.2-gene targeting is an effective approach for selective inhibition of functional expression of KATP channels.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4408-14
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Disruption of glucose sensing and insulin secretion by ribozyme Kir6.2-gene targeting in insulin-secreting cells.
pubmed:affiliation
Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, Georgia 30302-4010, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't