Glucose recruits K(ATP) channels via non-insulin-containing dense-core granules.
beta cells rely on adenosine triphosphate-sensitive potassium (K(ATP)) channels to initiate and end glucose-stimulated insulin secretion through changes in membrane potential. These channels may also act as a constituent of the exocytotic machinery to mediate insulin release independent of their electrical function. However, the molecular mechanisms whereby the beta cell plasma membrane maintains an appropriate number of K(ATP) channels are not known. We now show that glucose increases K(ATP) current amplitude by increasing the number of K(ATP) channels in the beta cell plasma membrane. The effect was blocked by inhibition of protein kinase A (PKA) as well as by depletion of extracellular or intracellular Ca(2+). Furthermore, glucose promoted recruitment of the potassium inward rectifier 6.2 to the plasma membrane, and intracellular K(ATP) channels localized in chromogranin-positive/insulin-negative dense-core granules. Our data suggest that glucose can recruit K(ATP) channels to the beta cell plasma membrane via non-insulin-containing dense-core granules in a Ca(2+)- and PKA-dependent manner.
Yang
Shao-Nian
SN
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden. shao-nian.yang@ki.se
Wenna
Nancy Dekki
ND
Yu
Jia
J
Yang
Guang
G
Qiu
Hua
H
Yu
Lina
L
Juntti-Berggren
Lisa
L
Köhler
Martin
M
Berggren
Per-Olof
PO
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002864:Chromogranins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism*; D000099161:Kcnj11 Channel
D002118:Calcium; D002864:Chromogranins; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D007328:Insulin; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D000099161:Kcnj11 Channel