Multiple Guanine Nucleotide Exchange Factors Mediate Glucose-Induced Rac1 Activation and Insulin Secretion: Is It Precise Regulatory Control or a Case of Two Peas from the Same Pod?

Glucose-stimulated insulin secretion involves G protein (Rac1)-mediated cytoskeletal remodeling and vesicular transport and fusion with the plasma membrane. Recent evidence implicates at least three guanine nucleotide exchange factors (GEFs), namely, Tiam1, Vav2, and P-Rex1, in glucose-induced activation of Rac1 and insulin secretion. This Viewpoint highlights potential mechanisms underlying Tiam1/Vav2/P-Rex1 sensitive Rac1-mediated insulin secretion in the glucose-stimulated β-cell.