Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea receptor.
Pancreatic alpha-cells, like beta-cells, express ATP-sensitive K(+) (K(ATP)) channels. To determine the physiological role of K(ATP) channels in alpha-cells, we examined glucagon secretion in mice lacking the type 1 sulfonylurea receptor (Sur1). Plasma glucagon levels, which were increased in wild-type mice after an overnight fast, did not change in Sur1 null mice. Pancreas perfusion studies showed that Sur1 null pancreata lacked glucagon secretory responses to hypoglycemia and to synergistic stimulation by arginine. Pancreatic alpha-cells isolated from wild-type animals exhibited oscillations of intracellular free Ca(2+) concentration ([Ca(2+)](i)) in the absence of glucose that became quiescent when the glucose concentration was increased. In contrast, Sur1 null alpha-cells showed continuous oscillations in [Ca(2+)](i) regardless of the glucose concentration. These findings indicate that K(ATP) channels in alpha-cells play a key role in regulating glucagon secretion, thereby adding to the paradox of how mice that lack K(ATP) channels maintain euglycemia.
Shiota
Chiyo
C
Vanderbilt University School of Medicine, Dept. of Molecular Physiology and Biophysics, Nashville, TN 37232-0615, USA.
Rocheleau
Jonathan V
JV
Shiota
Masakazu
M
Piston
David W
DW
Magnuson
Mark A
MA
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005934:Glucagon / Q000097:blood* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency*; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D005934:Glucagon; D005947:Glucose; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C577508:Abcc8 protein, mouse; C117780:mitochondrial K(ATP) channel