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Research Summary
Genetic basis of type 1 and Type 2 Diabetes Mellitus with specific emphasis on the cellular and molecular biology of the pancreatic beta cell.
Research Activities
The loss of pancreatic beta cell mass is central to the pathogenesis of diabetes mellitus. The objective of our research is to understand the cellular and molecular mechanisms controlling pancreatic beta cell mass in the setting of hyperglycemia and increased metabolic demand for insulin. We have chosen to study closely related inbred mouse strains with differential diabetes-susceptibility. The C57BL/6J (B6) animals successfully compensate for greater insulin resistance with increasing beta cell hyperplasia and hypertrophy producing a net proliferative response. In contrast, pancreatic islets of C57BLKS/J (KS) animals, when made obese, ultimately respond to increased insulin demand with progressive net beta cell depletion. Our studies suggest that KS islets fail to expand beta cell mass in response to excess glucose loads predisposing KS beta cells to increased metabolic stress and an early demise.
We have ongoing in vitro experiments using isolated islets in culture and microarray technology to generate differential expression profiles. We are currently systematically identifying beta cell-specific genes and signaling pathways that are responsible for the capacity of beta cells to survive and replicate in the setting of increased glycemic/metabolic stress. Knowledge of these genes and their signaling pathways will then be exploited to enhance beta cell production, survival and function in a hyperglycemic environment in efforts to ultimately to prevent or reverse the course of diabetes mellitus.
Selected Publications:
1. Brillantes, A.-M. B. and R. L. Leibel. (1999) Catalase and superoxide dismutase mRNA expression in skeletal muscle and adipose tissue of diabetes-resistant (C57BL/6J) and diabetes-susceptible (C57BLKs/J) mouse strains. 81st Annual Endocrine Society Meeting Abstracts
:2-22
2. Brillantes, A.-M. B. (2003) Case Study: Models for diabetes and prevention. Resident and Staff Physician
March Suppl:10-18
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