Thesis
Does serum from people with type 2 Diabetes cause insulin resistance in cultured cells?
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2026
- Thesis identifier
- T17998
- Person Identifier (Local)
- 202178408
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Type 2 diabetes (T2D) is a chronic metabolic condition characterised by insulin resistance that affects millions worldwide, leading to significant health complications like heart disease, kidney failure, and vision loss if not properly managed. Previous studies have shown that serum from people with T2D (PWT2D) can induce insulin resistance when applied to cultured cells, yet the identity and mechanism of action of the responsible circulating factor(s) remain unclear. The aim of this PhD project was to investigate the insulin-promoting capacity of serum from PWT2D using two complimentary functional assays and to explore the nature of the mediating humoral factor(s). Insulin-mediated repression of Pck1 transcript accumulation was assessed in H4-II-E hepatoma cells, and insulin-stimulated radiolabelled glucose uptake was measured in 3T3-L1 adipocytes. Both assays were validated and shown to be sensitive to experimentally induced insulin resistance. However, pooled serum from individuals with established, lifestyle-managed T2D did not induce detectable insulin resistance in either model. In contrast, preliminary experiments using serum from a small cohort of people with preT2D revealed a selective impairment in insulin-stimulated glucose uptake in 3T3-L1 adipocytes, without corresponding changes in proximal signalling through AKT or AS160. In a parallel study, age-related changes in 3T3-L1 adipocytes were characterised. As the cells aged, they adopted a more white adipose tissuelike morphology accompanied by selective reductions in several proteins involved in insulin signalling and GLUT4 trafficking. However, maximal insulin-stimulated glucose uptake remained unchanged, indicating functional resilience despite morphological remodelling. Overall, this thesis highlights that the insulin resistance-inducing activity of serum from PWT2D is highly dependent on donor disease stage. The selective impairment observed in adipocytes but not hepatomas raises questions about the potential tissue- or pathway-specific nature of the mediating humoral factor(s). The work provides a validated experimental platform for future identification of circulating mediators and contributes to our understanding of how humoral factors propagate insulin resistance in T2D.
- Advisor / supervisor
- Gould, Gwyn W.
- Resource Type
- DOI
- Date Created
- 2025
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PDF of thesis T17998 | 2026-05-13 | Public | Download |