The triggering pathway to insulin secretion: Functional similarities and differences between the human and the mouse cells and their translational relevance

In cells, stimulation by metabolic, hormonal, neuronal, and pharmacological factors is coupled to secretion of insulin through different intracellular signaling pathways. Our knowledge about the molecular machinery supporting these pathways and the patterns of signals it generates comes mostly from rodent models, especially the laboratory mouse. The increased availability of human islets for research during the last few decades has yielded new insights into the specifics in signaling pathways leading to insulin secretion in humans. In this review, we follow the most central triggering pathway to insulin secretion from its very beginning when glucose enters the cell to the calcium oscillations it produces to trigger fusion of insulin containing granules with the plasma membrane. Along the way, we describe the crucial building blocks that contribute to the flow of information and focus on their functional role in mice and humans and on their translational implications.