Type 2 diabetes affects nearly 19 million people in the United States. Despite conventional treatment, patients with this disease experience progressive beta-cell dysfunction, that may in part be due to beta-cell de-differentiation. We hypothesize that this de-differentiation of the beta-cell results from changes in chromatin structure that function to decrease euchromatin at the insulin gene. To test this hypothesis, the following aims are proposed: 1. Characterize insulin gene transcription in islets of mildly and overtly diabetic BTBR- ob mice. 2. Characterize insulin gene chromatin structure in islets of mildy and overtly diabetic BTBR-ob mice.
Aim 1 will be addressed by measuring glucose-stimulated insulin secretion and insulin gene transcription by real-time PCR. To address Aim 2, A quantitative real-time PCR based chromatin immunoprecipitation assay and micrococcal nuclease digest assay will be used. The long-term objective of this research is to gain an enhanced understanding of insulin gene transcription and chromatin structure in a mouse model of Type 2 DM, with the ultimate goal of applying this knowledge to human disease and the development of novel treatment strategies.
| Evans-Molina, Carmella; Regan, Susan; Henault, Lori E et al. (2007) The new Medicare Part D prescription drug benefit: an estimation of its effect on prescription drug costs in a Medicare population with atrial fibrillation. J Am Geriatr Soc 55:1038-43 |
| Evans-Molina, Carmella; Garmey, James C; Ketchum, Robert et al. (2007) Glucose regulation of insulin gene transcription and pre-mRNA processing in human islets. Diabetes 56:827-35 |
