olsonla@msu.edu
Phone: (517) 355-6475, ext. 1135
Home Department:
Physiology
Home Page: Physiology
Associate Professor of Physiology; Ph.D., University of Minnesota, 1991
Nutritional regulation of pancreatic beta cell function and gene expression.
Our research interests focus on the molecular mechanisms by which chronic exposure of pancreatic islets to elevated glucose concentrations adversely alter pancreatic beta cell function-the so called glucose toxicity hypothesis. We have identified that chronic exposure of pancreatic b cell lines to elevated glucose concentrations decreases insulin biosynthesis by decreasing the rate of insulin gene transcription. The decrease in insulin gene transcription results from a defect in the binding of two transcription factors that are essential to insulin gene transcription. We are currently investigating: (1) the molecular mechanisms responsible for the decrease in binding of these critical transcription factors, and (2) whether the decrease in insulin gene expression that occurs in animal models of type II diabetes mellitus is related to decreased binding of these transcription factors. Parallel projects also underway include studies design to investigate the mechanisms by which fatty acids and regulators of cell growth affect pancreatic beta cell function and gene expression.
Selected
Publications
Olson, L.K., A. Sharma, M. Peshavaria, C.V.E. Wright, H.C. Towle, R.P. Robertson, R. Stein. 1995. Reduction of insulin gene transcription in HIT-T15 b cells chronically exposed to a supraphysiological glucose concentration is associated with loss of STF-1 transcription factor expression. Proc. Natl. Acad. Sci., 92:9127-9131.
Olson, L.K., J. Qain, and V. Poitout. 1998. Glucose rapidly and reversibly decreases insulin gene transcription in INS-1 cells via decrements in binding activity of STF-1 and C1 activator. Mol. Endo. 12:207-219.
Qian, J., E. Newburg-Kaytor, H.C. Towle, and L.K. Olson. 1999. Functional regulation of Pdx-1 gene expression by upstream stimulatory factor, USF. Biochemical J. 341:315-322.