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1 Departments of Paediatrics,
2 Physiology and Pharmacology and
3 Medicine, University of Western Ontario, Canada
4 Childrens Health Research Institute, London, Ontario, Canada
(Requests for offprints should be addressed to C Pin, Department of Paediatrics, University of Western Ontario, Childrens Health Research Institute, London, Ontario N6C 2V5, Canada; Email: cpin{at}uwo.ca)
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 (Mist1KO) mice. Endocrine function was evaluated using a glucose-tolerance test on 210-month-old female mice and revealed a significant reduction in glucose-clearing ability in 10-month-old Mist1KO 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 Mist1KO mice was observed along with a decrease in Glut-2 protein accumulation. These results suggest that the islets in Mist1KO 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.
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A. S. Kowalik, C. L. Johnson, S. A. Chadi, J. Y. Weston, E. N. Fazio, and C. L. Pin Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1123 - G1132. [Abstract] [Full Text] [PDF] |
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