The Hippo Signaling Pathway in Pancreatic β-Cells: Functions and Regulations

Hippo signaling is an evolutionarily conserved pathway that critically regulates development and homeostasis of various tissues in response to a wide range of extracellular and intracellular signals. As an emerging important player in many diseases, the Hippo pathway is also involved in the pathophysiology of diabetes on the level of the pancreatic islets. Multiple lines of evidence uncover the importance of Hippo signaling in pancreas development as well as in the regulation of beta-cell survival, proliferation, and regeneration. Hippo therefore represents a potential target for therapeutic agents designed to improve beta-cell function and survival in diabetes. In this review, we summarize recent data on the regulation of the Hippo signaling pathway in the pancreas/in pancreatic islets, its functions on beta-cell homeostasis in physiology and pathophysiology, and its contribution toward diabetes progression. The current knowledge related to general mechanisms of action and the possibility of exploiting the Hippo pathway for therapeutic approaches to block beta-cell failure in diabetes is highlighted.