The obesity and diabetes epidemics
The obesity epidemic is evoking a parallel epidemic in metabolic
diseases, including diabetes, cardiovascular disease, hypertension,
fatty liver, neurological diseases, and kidney failure. Genetic factors
contribute to these diseases and obesity acts as a stressor that elicits
phenotypes that might otherwise be silent. Our laboratory uses genetics
to identify novel causal and responsive genes leading to metabolic
Diabetes results from an absolute or a relative insulin deficiency.
Pancreatic β-cells sense blood glucose and respond by secreting insulin.
Insulin lowers blood glucose by promoting its clearance from the
circulation and by inhibiting gluconeogenesis. In type 1 diabetes, there
is an absolute insulin deficiency due to autoimmune destruction of the
cells that produce insulin, the pancreatic β-cells. However, in type 2
diabetes, there is an increased requirement for insulin, caused by a
dampened response to the hormone, coupled with a failure to meet this
increased requirement. We study the mechanisms by which β-cells sense
glucose and trigger insulin secretion.
A novel gene responsible for biogenesis of insulin containing vesicles. We have identified a novel gene that is critical for the normal
formation of the dense core vesicles that transport insulin to the
plasma membrane for regulated exocytosis.
Tomosyn-2, a protein involved in insulin exocytosis. We recently
identified Tomosyn-2 as a gene involved in type 2 diabetes. It places a
brake insulin exocytosis. We are studying the signaling pathway that
releases this brake, leading to insulin secretion.
Gene causal networks and diabetes. By combining global gene
expression profiling and genetics, we are able to construct causal
networks linking specific genes with diabetes phenotypes. One of those
genes is the transcription factor NFATc2. We are studying its regulation
in relation to β-cell function and diabetes.
Molecular biology of ß-cell proliferation. We have identified
several factors involved in stimulating β-cell proliferation. We aim to
discover the receptors and the signaling pathways involved in this
critically important process.
Electron micrograph of a pancreatic beta-cell showing theabundance of dense core vesicles containing insulin.
Fluorescence micrograph of a pancreatic islet showing insulin-containing beta-cells (red) and glucagon-containing alpha-cells (green)