Linked Life Data

2647550

Source:http://linkedlifedata.com/resource/pubmed/id/2647550

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-5-4
pubmed:abstractText
It is accepted for insulin-secreting cells in culture that the closure of ATP-sensitive K+ channels causes the glucose-dependent depolarization of pancreatic beta-cells seen at subthreshold levels (less than 100 mg/dl) of glucose. The question remains for the more thoroughly studied beta-cells in freshly dissected intact islets, however, whether closure of these channels is responsible for subthreshold glucose-dependent depolarization and suprathreshold glucose-dependent regulation of membrane electrical activity. To answer this, we took advantage of the ability of tolbutamide, an orally active antidiabetic agent, to specifically inhibit ATP-sensitive K+ channels in pancreatic beta-cells to determine whether these channels are active at sub- and suprathreshold levels of glucose and whether channel closure by tolbutamide reproduces the electrophysiological effects of glucose stimulation. We recorded membrane electrical activity from freshly dissected adult mouse pancreatic islets exposed to various levels of glucose and tolbutamide. As previously found by others, tolbutamide depolarizes islet cells in the absence of glucose, but we have found that, although the depolarization can trigger Ca2+ action potentials (spikes), a glucose-dependent permissive factor may be required for the normal bursting pattern of spiking. More significantly, we found that, unlike other beta-cell stimuli, tolbutamide specifically mimics the effects of glucose stimulation on the pattern of suprathreshold electrical activity. The effects were seen with levels of tolbutamide that correspond to those required to inhibit ATP-sensitive K+ channels. These data suggest that ATP-sensitive K+ channels are active at sub- and suprathreshold levels of glucose and may be the sole pathway by which either glucose or tolbutamide depolarizes beta-cells and controls beta-cell electrical activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
416-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Tolbutamide as mimic of glucose on beta-cell electrical activity. ATP-sensitive K+ channels as common pathway for both stimuli.
pubmed:affiliation
Division of Metabolism, Seattle VA Medical Center, WA 98108.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.