Glucose-induced changes of the ATP / ADP-Ratio in alpha- and beta-cells

Background and aims The question was whether the increase of glucagon secretion upon glucose lowering is an intrinsic function of the alpha-cell and if so, whether this effect is at the level of the glucose metabolism or electrical events of the plasma membrane.

Methods Insulin- and glucagon-secretion were simultaneously measured by perfusion of mouse islets and ELISA. To obtain single alpha-cells, islets were incubated with Alloxan before dissociation into single cells. Alpha- and beta-cells were adenovirally transduced with the fluorescent adenine nucleotide indicator PercevalHR. The indicator SNARF was used for pH-correction, the PercevalHR / SNARF ratio was a semiquantitative measure of the ATP / ADP-Ratio.

Results Upon lowering the glucose concentration from 5 to 1 mM alpha-cells showed a transient increase in the ATP / ADP-Ratio from 4.8 to 5.4. In beta-cells, only a monotonous decrease was seen. Raising glucose from 1 to 30 mM resulted in an increase of the ratio value by ca. 1.1 in alpha-cells. After an initial peak, an elevated plateau lasted as long as 30 mM glucose was present. In beta-cells, the initial increase by 30 mM glucose had a threefold larger amplitude, followed by a slow further increase. Intriguingly, the transient increase of the ratio value in alpha-cells upon lowering of the glucose concentration was paralleled by a transient increase of the glucagon secretion in perifused islets. This increase occurred well before the insulin secretion decreased.

Conclusion The paradox glucagonotropic effect of low glucose may be an intrinsic property of the alpha-cell involving a transient increase of the ATP / ADP-Ratio.

Publication History

Article published online:
06 May 2021