Glucose and pharmacological modulators of ATP-sensitive K+ channels control [Ca2+]c by different mechanisms in isolated mouse alpha-cells.
OBJECTIVE
We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell [Ca(2+)](c).


METHODS
GYY mice (expressing enhanced yellow fluorescent protein in alpha-cells) and NMRI mice were used. [Ca(2+)](c), the K(ATP) current (I(KATP), perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single alpha-cells and, for comparison, in single beta-cells.


RESULTS
In 0.5 mmol/l glucose, [Ca(2+)](c) oscillated in some alpha-cells and was basal in the others. Increasing glucose to 15 mmol/l decreased [Ca(2+)](c) by approximately 30% in oscillating cells and was ineffective in the others. alpha-Cell I(KATP) was inhibited by tolbutamide and activated by diazoxide or the mitochondrial poison azide, as in beta-cells. Tolbutamide increased alpha-cell [Ca(2+)](c), whereas diazoxide and azide abolished [Ca(2+)](c) oscillations. Increasing glucose from 0.5 to 15 mmol/l did not change I(KATP) and NAD(P)H fluorescence in alpha-cells in contrast to beta-cells. The use of nimodipine showed that L-type Ca(2+) channels are the main conduits for Ca(2+) influx in alpha-cells. gamma-Aminobutyric acid and zinc did not decrease alpha-cell [Ca(2+)](c), and insulin, although lowering [Ca(2+)](c) very modestly, did not affect glucagon secretion.


CONCLUSIONS
alpha-Cells display similarities with beta-cells: K(ATP) channels control Ca(2+) influx mainly through L-type Ca(2+) channels. However, alpha-cells have distinct features from beta-cells: Most K(ATP) channels are already closed at low glucose, glucose does not affect cell metabolism and I(KATP), and it slightly decreases [Ca(2+)](c). Hence, glucose and K(ATP) channel modulators exert distinct effects on alpha-cell [Ca(2+)](c). The direct small glucose-induced drop in alpha-cell [Ca(2+)](c) contributes likely only partly to the strong glucose-induced inhibition of glucagon secretion in islets.
Quoix
Nicolas
N
Unit of Endocrinology and Metabolism, University of Louvain Faculty of Medicine, Brussels, Belgium.
Cheng-Xue
Rui
R
Mattart
Laurine
L
Zeinoun
Ziad
Z
Guiot
Yves
Y
Beauvois
Mélanie C
MC
Henquin
Jean-Claude
JC
Gilon
Patrick
P
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009249:NADP / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001386:Azides; D054086:KATP Channels; D009249:NADP; D005680:gamma-Aminobutyric Acid; D009553:Nimodipine; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D002118:Calcium