Glucose and Pharmacological Modulators of ATP-Sensitive K+ Channels Control [Ca2+]c by Different Mechanisms in Isolated Mouse α-Cells
Open Access
- 1 February 2009
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 58 (2), 412-421
- https://doi.org/10.2337/db07-1298
Abstract
OBJECTIVE—We studied how glucose and ATP-sensitive K+ (KATP) channel modulators affect α-cell [Ca2+]c. RESEARCH DESIGN AND METHODS—GYY mice (expressing enhanced yellow fluorescent protein in α-cells) and NMRI mice were used. [Ca2+]c, the KATP current (IKATP, perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single α-cells and, for comparison, in single β-cells. RESULTS—In 0.5 mmol/l glucose, [Ca2+]c oscillated in some α-cells and was basal in the others. Increasing glucose to 15 mmol/l decreased [Ca2+]c by ∼30% in oscillating cells and was ineffective in the others. α-Cell IKATP was inhibited by tolbutamide and activated by diazoxide or the mitochondrial poison azide, as in β-cells. Tolbutamide increased α-cell [Ca2+]c, whereas diazoxide and azide abolished [Ca2+]c oscillations. Increasing glucose from 0.5 to 15 mmol/l did not change IKATP and NAD(P)H fluorescence in α-cells in contrast to β-cells. The use of nimodipine showed that L-type Ca2+ channels are the main conduits for Ca2+ influx in α-cells. γ-Aminobutyric acid and zinc did not decrease α-cell [Ca2+]c, and insulin, although lowering [Ca2+]c very modestly, did not affect glucagon secretion. CONCLUSIONS—α-Cells display similarities with β-cells: KATP channels control Ca2+ influx mainly through L-type Ca2+ channels. However, α-cells have distinct features from β-cells: Most KATP channels are already closed at low glucose, glucose does not affect cell metabolism and IKATP, and it slightly decreases [Ca2+]c. Hence, glucose and KATP channel modulators exert distinct effects on α-cell [Ca2+]c. The direct small glucose-induced drop in α-cell [Ca2+]c contributes likely only partly to the strong glucose-induced inhibition of glucagon secretion in islets.Keywords
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