Thesis

MicroRNA-191: regulator of pancreatic beta cell stress response

Diabetes is one of the United States’ worst epidemics; the dangers associated with the disease can be both fatal and varied. The constant presence of high concentrations of glucose and free fatty acids (FFA) becomes a source of stress for cells, which results in programmed cell death (apoptosis). Our lab has identified a microRNA (miRNA), miR- 191, that may be involved in the stress response of pancreatic beta cells. miRNAs have been recognized as key regulators of the translation of messenger RNA (mRNA). miRNAs are involved in virtually all cellular processes, have the ability to target multiple genes, and play important roles in diseases such as cancer and diabetes. Previous research suggested that miR-191 is under the control of the pancreatic and duodenal homeobox 1 transcription factor (PDX-1) and of the neurogenic differentiation 1 transcription factor (NeuroD1), both of which are regulated in the presence of glucose. I have also observed that miR-191 is up-regulated when rat insulinoma cells (INS-1) are treated with glucose. Bioinformatic analysis suggests possible roles for miR-191 in regulating apoptotic genes. Inhibiting miR-191 in a UV-induced stress assay in insulinoma (INS-1) cells results in decreased cell death. Decreased cell death was also observed when miR-191 was knocked down in samples that were treated with 30 mM glucose and 0.5 mM palmitate. It is not yet clear how miR-191 is involved in the beta cell stress response but based on data presented here it appears that miR-191 is promoting apoptosis in response to stressful conditions.

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