Electrical activity-triggered glucagon-like peptide-1 secretion from primary XXXX L-cells.

@entity37400 @entity972 @entity6 @entity1160 @entity19 @entity20647 @entity1022 @entity1372 @entity34072 @entity460 @entity594
@entity20647 ( @entity20647 ) based therapies are now widely used for the treatment of type 2 @entity6 . Developing our understanding of intestinal @entity20647 release may facilitate the development of new therapeutics aimed at targeting the @entity20647 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated @entity1372 and @entity460 channels for @entity20647 secretion. Primary @entity19 L-cells were identified and purified using @entity19 expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. @entity20647 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated @entity1372 currents, inhibition of which by @entity1022 reduced both basal and @entity1160 -stimulated @entity20647 secretion. Voltage gated @entity460 channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that @entity20647 release was blocked both by @entity594 and   -conotoxin MVIIC. We observed large voltage-dependent @entity972 currents, but only a small @entity34072 sensitive current that might be attributable to @entity37400 . @entity20647 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type @entity460 currents. The concept of an electrically excitable L-cell provides a basis for understanding how @entity20647 release may be modulated by nutrient, hormonal and pharmaceutical stimuli.
