FIGURE 8.

Roles of Hes3 in pancreatic islet function. A, MIN6 cells can be cultured under different culture conditions, in which the role of Hes3 varies. B, potentially relevant signaling pathways that may intercept with Hes3 include the leptin signaling system and irradiation-induced stresses. In genetic models of leptin signaling disruption (ob/ob and db/db mouse strains), Hes3 induction in the pancreatic duct is observed. Likewise in wild-type mice subjected to total body irradiation. C, Hes3 null mice appear normal with no obvious phenotype. Upon challenge with STZ, however, phenotypes are revealed, including earlier increases in blood glucose levels and a decreased number of beta cells in the islet, relative to wild-type controls.