Scientific Presentations Summer 2009 - Dana-Farber/Harvard ...

Repression Of Transcription Factor 7-Like 2 Increases Risk Of Type 2 Diabetes
Tsega Meshesha
Mentor: Melissa K. Thomas, MD, PhD
Massachusetts General Hospital
Diabetes mellitus is a disorder characterized by hyperglycemia that can occur through
mechanisms such as impaired insulin secretion, insulin resistance in peripheral tissues
and increased glucose output by liver. Genome-wide association studies have identified
Transcription factor 7-like 2 (TCF7L2), a key element of the Wnt signaling
pathway, as a genetic variant linked to a higher risk of developing type 2 diabetes.
However, the mechanisms by which TCF7L2 is implicated in this disease are unknown.
The objective of this study is to determine whether TCF7L2 deficiency alters
pancreatic beta cell mass, function or insulin production. To address this question,
we are investigating the phenotype of TCF7L2 heterozygous knockout as compared
to wild-type control mice. The mice were genotyped by extracting DNA from tail
biopsies. The extracted DNA was analyzed by polymerase chain reaction (PCR). To
determine whether TCF7L2 deficiency alters insulin production and pancreatic architecture,
pancreatic tissues from TCF7L2 heterozygote and wild-type mice were
immunostained for TCF7L2, insulin, and glucagon. It is expected that if TCF7L2
regulates pancreatic endocrine cell mass or hormone production, the immunostaining
will reveal a change in beta and/or alpha cell mass or pancreatic hormone expression
patterns when pancreatic tissue of TCF7L2 heterozygotes is compared to controls.
This study may elucidate how TCF7L2 influences and/or regulates glucose levels.