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ABSTRACT: Objective
We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell [Ca(2+)](c).Research design and 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.
SUBMITTER: Quoix N
PROVIDER: S-EPMC2628615 | biostudies-literature | 2009 Feb
REPOSITORIES: biostudies-literature
Quoix Nicolas N Cheng-Xue Rui R Mattart Laurine L Zeinoun Ziad Z Guiot Yves Y Beauvois Mélanie C MC Henquin Jean-Claude JC Gilon Patrick P
Diabetes 20081113 2
<h4>Objective</h4>We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell [Ca(2+)](c).<h4>Research design and methods</h4>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.<h4>Results</h4>In 0.5 mmol/l glucose, [Ca(2+)](c) oscillated i ...[more]