"DEVELOPMENT AND FUNCTION OF PANCREATIC BETA-CELLS IN C-KITwv MUTANT MI" by Farzam Ayazi

Author

Farzam Ayazi

Date of Award

2006

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Rennian Wang

Abstract

Islet transplantation is a potential cure for diabetes. To overcome the limited availability of transplantable islets, finding factors which promote survival and differentiation of precursor cells into beta-cells is essential. One potential factor is c-Kit receptor tyrosine kinase (c-Kit). This research examined morphology and function of pancreatic beta cells in c-Kitw'v mutant mice, which have nonfunctional c-Kit. At 8-weeks, the male c KitW-v/ mice showed high fasting blood glucose levels and became glucose intolerant which was associated with low levels of plasma insulin concentration after glucose stimulation. Morphometric analysis revealed that both islet- and beta-cell mass were significantly reduced in the male c-KitW-v/ mice, which paralleled the reduction of the pancreatic insulin content as well as Pdx-1 and insulin gene expression. These changes were not observed in female c-KitW-v/t mice up to 40-weeks of age. In conclusion, lack of a functional c-Kit receptor affects beta-cell mass and disrupts beta-cell development and function.

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