Altered Glut-2 accumulation and beta-cell function in mice lacking the exocrine-specific transcription factor, Mist1.

Mist1 is an exocrine-specific transcription factor that is necessary for the establishment of cell organization and function of pancreatic acinar cells. While Mist1 is not expressed in the endocrine pancreas, the disorganized phenotype of the exocrine component may affect endocrine function. Therefore, we examined endocrine tissue morphology and function in Mist1-knockout (Mist1(KO)) mice. Endocrine function was evaluated using a glucose-tolerance test on 2-10-month-old female mice and revealed a significant reduction in glucose-clearing ability in 10-month-old Mist1(KO) mice compared with wild-type mice. Immunohistochemical analysis of islet hormone expression indicated that the decreased endocrine function was not due to a decrease in insulin-, glucagon- or somatostatin-expressing cells. However, a decrease in the size of islets in 10-month-old Mist1(KO) mice was observed along with a decrease in Glut-2 protein accumulation. These results suggest that the islets in Mist1(KO) mice are functionally compromised, likely accounting for the decreased glucose tolerance. Based on these findings, we have identified that the loss of a regulatory gene in the exocrine compartment can affect the endocrine component, providing a possible link between susceptibility for various pancreatic diseases.