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BACKGROUND/OBJECTIVES: The purpose of the current study was to determine whether increased physical activity (PA) altered glycemic control while ingesting an energy-balanced high-fructose diet. SUBJECTS/METHODS: Twenty -two normal-weight men and women (age: 21.2 ± 0.6 years; body mass index: 22.6 ± 0.6kg/[m.sup.2]) participated in a randomized, cross-over design study in which they ingested an additional 75 g of fructose for 14 days while either maintaining low PA (FR+inactive) (< 4500 steps/day) or high PA (FR+active) (> 12 000 steps/day). Before and following the 2-week loading period, a fructose-rich meal challenge was administered and blood was sampled at baseline and for 6 h after the meal and analyzed for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), c-peptide, glucose and insulin concentrations. RESULTS: Plasma insulin, glucose, c-peptide, GIP and GLP-1 concentrations significantly increased in response to the test meal on all test visits (P < 0.05). C-peptide incremental area under the curve (AUC) decreased by 10 208 ± 120 pmol/l x min for 6 h from pre to post Fr+active intervention (P = 0.02) leading to a decrease in plasma insulin total AUC (pre: 58 470.2 ± 6261.0 pmol/l; post: 49 444.3 ± 3883.0 pmol/l; P = 0.04) resulting in a decrease Apeak[Insulin] (P = 0.009). Following the FR+active intervention, GIP total AUC significantly decreased (P = 0.005) yet only males had a lower total GLP-1 AUC after both interventions (P = 0.049). There were no sex differences in GIP levels. CONCLUSIONS: Increased PA attenuates the deleterious effects on glycemic control caused by a high-fructose diet. These changes in glycemic control with PA are associated with decreases in insulin and GIP concentrations. European Journal of Clinical Nutrition (2014) 68, 1048-1054; doi: 10.1038/ejcn.2014.90; published online 21 May 2014, INTRODUCTION Although regular physical activity (PA) has undisputed health benefits, the majority of Americans do not meet the minimum PA guidelines (1) and there are recognized deleterious effects of low [...]