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Browsing by study line "Solu- ja systeemifysiologia"

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  • Lackman, Madeleine Helena (2022)
    Diabetes mellitus is an incurable disease caused by dysfunctional insulin signaling. The brown adipose tissue (BAT) serves as a hotspot for both lipid and glucose consumption and is thus an attractive target for treating metabolic diseases. Newly surfacing evidence suggest that the endothelial cells (ECs) lining the inner layer of vessels might regulate the morphology and function of adipose tissues. Several studies, including our own, suggest that the vessel density is negatively affected by metabolic diseases. As the BAT is an important organ for systemic lipid and glucose metabolism, and as the effects of metabolic diseases on BAT vessels are not adequately explored, I wanted to investigate how the BAT vasculature changes upon early time points of type 1 (T1D) and 2 (T2D) diabetes in this thesis work. To this end, I used mouse models with chemically induced T1D and genetic T2D and characterized these models with immunohistochemical analyses and immunoassays. To explore the transcriptomic landscapes of ECs and adipose stem cells (ASCs), I analyzed scRNAseq data of BAT stromal vascular fractions (SVF), focusing on changes in gene expression and EC-ASC interactions at a transcriptomic level. Also, by using a publicly available single-cell RNA sequencing (scRNAseq) dataset, I compared BAT SVF gene expression to complement the data resulting from our experiments. The results from this work reveal differential angiogenic responses in the T1D and T2D mouse models and open new avenues of research into how these different pathways are activated and how we can take advantage of these differences to treat diseases. All in all, this work will support the efforts in developing better options for future diabetes prevention, diagnosis, and care.