Date of Award
2024
Document Type
Campus Access Master's Thesis
Degree Name
Master of Science in Biological Sciences (MS)
Administrative Home Department
Department of Biological Sciences
Advisor 1
Xiaoqing Tang
Committee Member 1
Brigitte Morin
Committee Member 2
Ashutosh Tiwari
Committee Member 3
Thomas Werner
Abstract
Type 2 diabetes (T2D) is a chronic metabolic disorder marked by elevated blood glucose levels. Pancreatic β-cells regulate insulin production and secretion in response to glucose levels. MicroRNAs (miRNA) are small non-coding RNAs that govern β-cell function amid metabolic changes. We previously identified that mice with a β-cell-specific deletion of miR-483 exhibited high-fat diet (HFD)-induced hyperglycemia and reduced glucose tolerance. In this study, we investigated how miR-483 deficiency induces mitochondrial dysfunction in pancreatic β-cells. We discovered that miR-483 deficiency elevated enzymes linked to oxidative stress, lipid peroxidation, and bile acid synthesis and decreased mitochondrial respiration and ATP production rates, measured by the Seahorse Extracellular Flux Analyzer. Our data indicates that miR-483 is important in preserving mitochondrial function, and its loss initiates oxidative stress and subsequent β-cell dedifferentiation, contributing to T2D pathogenesis. These findings enhance our comprehension of T2D mechanisms and propose potential therapeutic targets for mitigating mitochondrial dysfunction in diabetes.
Recommended Citation
Sempek, Ellianna S., "LOSS OF MIR-483 IMPAIRS MITOCHONDRIAL FUNCTION IN PANCREATIC ISLETS", Campus Access Master's Thesis, Michigan Technological University, 2024.