Global Analysis of Metabolic Fluxes of Glucose and Glutamine in INS-1 Cells Exposed to Arsenite Using ¹³ C-Isotopic Tracers

Human exposure to arsenic has been reported to induce metabolic disorders in pancreatic β-cells. However, metabolic fluxes of essential carbon sources in pancreatic β-cells under arsenic exposure were not quantitatively characterized. In this study, 13C-labeled glucose and glutamine were used as the tracers to examine their fates in INS-1 832/13 cells treated with arsenite (iAsIII). INS-1 832/13 cells exposed to three concentrations of iAsIII (0.05, 0.5, and 1.0 μg/mL) maintained at least 80.0% of cell viability in comparison to the controls. Glucose uptake of INS-1 832/13 cells exposed to 1.0 μg/mL iAsIII was approximately 2 times higher than that of the controls. Accordingly, glucose was also accumulated in the iAsIII-treated INS-1 832/13 cells. The activities of glucose-derived pathways in INS-1 832/13 cells, including glycolysis, tricarboxylic acid (TCA) cycle, and pentose phosphate pathway (PPP), were consistently enhanced by iAsIII. However, mitochondrial respiratory indexes of INS-1 832/13 cells, including oxygen consumption rate (OCR), ATP-linked OCR, basal OCR, maximal respiration, and spare respiratory capacity, were considerably suppressed by iAsIII. Inhibitive effects of iAsIII on metabolic pathway activities of glutamine were observed. Collectively, our results suggest that iAsIII exposure can induce metabolic reprogramming involved with glucose and glutamine in INS-1 832/13 cells.