Defense Date


Document Type


Degree Name

Master of Science



First Advisor

Young-Jai You


Caenorhabditis elegans has been studied as a model organism in various areas of biomedical research because it shares many conserved functions at molecular and genetic levels with humans. Specifically, it is an ideal organism to study heterogeneous metabolic syndromes such as Type 2 Diabetes Mellitus (T2DM) as C. elegans can be used to delineate molecular pathways that are at the core of its problems. A growing number of populations worldwide are faced with chronic T2DM, which also manifests several complications, such as blindness, neuropathy and cardiovascular diseases. Currently, metformin is the first-line drug of choice administered to treat T2DM. While the mechanism by which it alleviates the symptoms of diabetes is unknown, it has been found to reduce metabolic rate by partially inhibiting the mitochondrial complex I in mammals. Using C. elegans as a genetic model organism, we show that metformin reduces the mitochondrial activity through endosomal Na+/H+ exchanger, which a previous lab member has found to be a potential target of metformin. Furthermore, we show that high glucose diet−known to reduce the worm’s lifespan−alter the endosomal-lysosomal system and autophagy, providing insights to using C. elegans as a diabetic model. Based on these results, we propose that C. elegans can serve as a model organism to study T2DM as well as provide new ways to further investigate the pathophysiology of this disease.


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