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 byinsulin resistance that affects millions worldwide, leading to significanthealth complications like heart disease, kidney failure, and vision loss if notproperly managed. Previous studies have shown that serum from people withT2D (PWT2D) can induce insulin resistance when applied to cultured cells,yet the identity and mechanism of action of the responsible circulatingfactor(s) remain unclear. The aim of this PhD project was to investigate theinsulin-promoting capacity of serum from PWT2D using two complimentaryfunctional assays and to explore the nature of the mediating humoralfactor(s).Insulin-mediated repression of Pck1 transcript accumulation was assessed inH4-II-E hepatoma cells, and insulin-stimulated radiolabelled glucose uptakewas measured in 3T3-L1 adipocytes. Both assays were validated and shownto be sensitive to experimentally induced insulin resistance. However,pooled serum from individuals with established, lifestyle-managed T2D didnot 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 in3T3-L1 adipocytes, without corresponding changes in proximal signallingthrough AKT or AS160.In a parallel study, age-related changes in 3T3-L1 adipocytes werecharacterised. As the cells aged, they adopted a more white adipose tissuelike morphology accompanied by selective reductions in several proteinsinvolved in insulin signalling and GLUT4 trafficking. However, maximalinsulin-stimulated glucose uptake remained unchanged, indicating functionalresilience despite morphological remodelling.Overall, this thesis highlights that the insulin resistance-inducing activity ofserum from PWT2D is highly dependent on donor disease stage. The selectiveimpairment observed in adipocytes but not hepatomas raises questions aboutthe potential tissue- or pathway-specific nature of the mediating humoralfactor(s). The work provides a validated experimental platform for futureidentification of circulating mediators and contributes to our understandingof how humoral factors propagate insulin resistance in T2D.
- Advisor / supervisor
- Gould, Gwyn W.
- Resource Type
- DOI
- Date Created
- 2025
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