A dynamic interaction between GTPases ras and rap determines signaling in beta-cells

Glucose and the incretin hormone glucagon-like peptide-1 (GLP-1) act synergistically as growth factors for insulin-producing b-cells by unknown mechanisms. We examined the involvement of small GTPases ras and rap1 to mitogenic signaling in the b-cell line INS-1E and primary human b-cell preparations. Here, we show that at unfavourable conditions for b-cell growth such as low glucose concentration (2.5 mM), ras is the major activator of MAPK and CREB signaling whereas contribution of rap to MAPK and CREB is minor or even inhibitory to signaling by ras. In contrast, when b-cells are cultivated at favourable growth…