Effects of Starvation on Matrix-Metalloproteinase 2 Expression in the Larval fat body of Drosophila melanogaster



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Insulin sensitivity declines with age in mammals, leading to diseases such as type 2 diabetes and obesity, yet the precise mechanism is not well understood. The modulation of insulin signaling is implicated in the pathogenesis of the diseases and plays a critical role in various metabolic processes. The matrix-metalloproteinase (MMP) are a family of multifunctional Zn2+-dependent protease enzymes that play a role in tissue development, cell organization, and cell cycle control in mammals and the model organism Drosophila melanogaster which are a great model organism for research because it has a rapid life cycle, is small and easily cultured, male and female individuals are easily differentiated, and they share 75% similarity to all human genes implicated in disease. (Guo et al., 2022). Many MMPs are attached to the cell membrane by the protein glycosylphosphatidylinositol (GPI), which allows them to interact with the extracellular matrix (ECM). In Drosophila there are two MMPs: MMP1 and MMP2 which together degrade ECM components (Jia et al., 2014). I investigated the role of MMPs in the regulation of insulin signaling. Past studies have examined the indirect involvement of Drosophila MMP2 in insulin signaling (Bond, 2010). Along with a homolog for MMP2, MMP14 direct cleavage of insulin receptor in a murine model, consequently suppressing insulin signaling. In my investigation, I studied the role of MMP2 in insulin signaling during larval development by performing starvation experiments. I hypothesize that starvation induces MMP2 expression to allow MMP2 to cleave insulin receptor, which shuts off insulin signaling, allowing autophagy and nutrient release to occur. In order to test this hypothesis I have examined MMP2 transcript levels in the fat bodies of fed and starved third instar larvae using real time quantitative Polymerase Chain Reaction (PCR). The results of my experiments support my hypothesis that higher MMP2 transcript levels are observed in a starved condition compared to a fed control.



MMP2, Insulin regulation, Drosophila melanogaster