Gupta Lab Research
Islet beta cells comprise the central regulatory tissue of the glucose homeostasis. A fine regulation of glucose homeostasis is achieved by precisely regulated insulin biosynthesis and secretion driving production and utilization of glucose by various tissues such as liver. Under normal or altered metabolic milieus when insulin sensitivity fluctuates, precise compensatory changes in insulin secretion are achieved by adaptive gain in beta cell mass and function.
The long-range objective of my laboratory is to elucidate the role of transcription factors as molecular switches in regulation of islet ß cell compensation and the mechanisms of de-compensation causing islet beta cell dysfunction in the setting of insulin resistance and T2DM. My scientific curiosity includes:
(a) Mapping out the active transcriptome of the islet beta cell's compensatory response to cope up with changing metabolic environments
(b) Identify the physiologically relevant pathways of the adaptive islet beta cell response that can be activated by pharmaceutical agents to preserve beta cell function and mass in individuals who have lost this capacity.
We use variety of bioinformatics tools to generate molecular models of transcriptional networks in islet beta cells and evaluate their target specificity by performing nuclear binding assays, chromatin immunoprecipitation, site-directed mutagenesis, and reporter assays. The physiological relevance of islet transcriptional machinery is tested by in vitro knockdown assays using RNAi in beta cell lines and conditional knockout animal models along with established animal models of obesity and acute beta cell loss. The specific collaborative projects include:
- Epigenetic regulation of islet beta cell signaling.
- Molecular mechanisms of adaptive islet beta cell responses towards ER and oxidative stress.
- Neuronal regulation of islet beta cell function and survival.
- Regulation of islet beta cell proliferation.