Increased ATP-sensitive K+ channel expression during acute glucose deprivation.
ATP-sensitive potassium (KATP) channels play a central role in glucose-stimulated insulin secretion (GSIS) by pancreatic beta-cells. Activity of these channels is determined by their open probability (Po) and the number of channels present in a cell. Glucose is known to reduce Po, but whether it also affects the channel density is unknown. Using INS-1 model beta-cell line, we show that the expression of K(ATP) channel subunits, Kir6.2 and SUR1, is high at low glucose, but declines sharply when the ambient glucose concentration exceeds 5mM. In response to glucose deprivation, channel synthesis increases rapidly by up-regulating translation of existing mRNAs. The effects of glucose deprivation could be mimicked by pharmacological activation of 5'-AMP-activated protein kinase with 5-aminoimidazole-4-carboxamide ribonucleotide and metformin. Pancreatic beta-cells which have lost their ability for GSIS do not show such changes implicating a possible (patho-)physiological link between glucose-regulated KATP channel expression and the capacity for normal GSIS.
Smith
Andrew J
AJ
Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK.
Partridge
Christopher J
CJ
Asipu
Aruna
A
Mair
Lindsey A
LA
Hunter
Malcolm
M
Sivaprasadarao
Asipu
A
D055372:AMP-Activated Protein Kinases; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D017077:Culture Media, Conditioned; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D005947:Glucose / Q000172:deficiency* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000096:biosynthesis; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D055372:AMP-Activated Protein Kinases; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D017077:Culture Media, Conditioned; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D005947:Glucose; D007328:Insulin; D009097:Multienzyme Complexes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; C484274:KCNJ5 protein, human