Högskolan i Skövde

Type 1 diabetes (T1D) arises from immune-mediated destruction of pancreatic β-cells; rising incidence implicates environmental and metabolic contributors. Prospective metabolomic studies have identified altered circulating amino-acid profiles, notably elevated glutamine and proline, preceding the first islet autoantibody in children who later develop T1D. This thesis tested whether supraphysiological extracellular concentrations of L-proline and L-glutamine increase glucose consumption by innate immune cells and activate nutrient-sensing signaling pathways, particularly the mTOR axis. Human THP-1 monocytic cells were exposed to baseline (1×), 2×, and 5× concentrations of either L-glutamine or L-proline; glucose uptake/consumption was estimated from residual medium glucose at 1 hour (with an additional ±FBS, ±insulin comparison at 24 and 48 hours). Secondary outcomes were RPS6KB1 and NFE2L2 transcript levels by RT-qPCR (48 hours) and cell viability by MTS (48 hours). Contrary to the hypothesis, 5× proline and 5× glutamine was associated with higher residual glucose at 1 hour (reduced net glucose uptake/consumption), while RPS6KB1 and NFE2L2 transcript levels showed no statistically significant differences across treatments. These findings indicate that acute extracellular amino-acid elevation alters glucose utilization in THP-1 cells under the tested conditions and motivates follow-up studies using protein-level and metabolic-flux readouts.