The goal of this research project is to understand how a high sugar diet may affect pancreatic beta cell function. High glucose concentrations lead to an increase in lipid droplets and TORC1 in beta cells, which promote high basal secretion of insulin (Erion K.A. et al., JBC, 2015). SREBP is a key regulator of cholesterol and lipid synthesis and depends on TORC1 activity. The active form of SREBP is located in the nucleus.
Does glucose-induced lipid synthesis in beta cells increase via SREBP? To answer this question, we propose: 1) To test the effect of high glucose (11mM) on nuclear SREBP in INS-1 cells in comparison to physiological glucose (4mM). 2) To determine if nuclear SREBP is affected when PIP4Kgamma (a regulator of TORC1) is suppressed.
SREBP translocation from the cytosol to the nucleus was measured by immunofluorescence. SREBP processing was measured by western blot. SREBP1 activation increased in response to prolonged exposure to excess glucose after at least 48hrs. Both translocation and processing increased in 11mM glucose compared to 4mM glucose. When PIP4Kgamma was suppressed in INS-1 cells, SREBP translocation was inhibited. Lipid droplet accumulation was measured by nile red staining and it was found that de novo lipid synthesis only contributes to a small fraction of total lipid droplets.
In conclusion, SREBP is activated in beta cells when in excess glucose. This may allow for lipid accumulation and basal hypersecretion of insulin due to over nutrition.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/23802 |
| Date | 12 July 2017 |
| Creators | Jakkilinki, Phani Deepti |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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