The biological responses of the transforming growth factor-β (TGF-β) superfamily, which includes Activins and Nodal, are induced by activation of a receptor complex and Smads. A type I receptor, which is a component of the complex, is known as an activin receptor-like kinase (ALK); currently seven ALKs (ALK1-ALK7) have been identified in humans. Activins signaling, which is mediated by ALK4 and 7 together with ActRIIA and IIB, plays a critical role in glucose-stimulated insulin secretion, development/neogenesis, and glucose homeostatic control of pancreatic endocrine cells; the insulin gene is regulated by these signaling pathways via ALK7, which is a receptor for Activins AB and B and Nodal. This review discusses signal transduction of ALKs in pancreatic endocrine cells and the role of ALKs in insulin gene regulation.