BackgroundGlycosylphosphatidylinositol-specific phospholipase D (GPLD1) is responsible for cleaving membrane-associated glycosylphosphatidylinositol (GPI) molecules, which is affected by diabetes. We aimed to examine the effect of 14 weeks treadmill running on serum GPLD1 levels and its association with glycemic indexes and serum glypican-4 (GPC-4), a novel GPI-anchored adipokine, in streptozotocin-nicotinamide-induced diabetic rats.MethodsThirty-six male Wister rats were randomly divided into three groups of twelve animals each, involving sedentary control (SC), sedentary diabetic (SD), and trained diabetic (TD) groups. The diabetes was induced through intraperitoneal injection of 120 mg/kg nicotinamide 15 min prior to intraperitoneal injection of 65 mg/kg streptozotocin in SD and TD groups. The TD group was exercised on a treadmill for 60 min/days, 5 days/wk at 26 m/min, and zero grade for 14 weeks. Following the experiment period, blood samples were taken from all animals and analyzed for experimental indexes via sandwich ELISA.ResultsExercise training caused a significant decrease in the elevated blood glucose levels and a significant increase in the lowered blood insulin levels in TD rats (both p < 0.001). Glucose tolerance of TD rats significantly improved following experimental protocol, as indicated by OGTT (p < 0.001). Experimental diabetes significantly increased serum GPLD1 levels (p < 0.001), while exercise training significantly decreased its levels (p < 0.001). Serum GPLD1 levels correlated directly with glycemic indexes involving FBS, 2hOGTT, and AUC of glucose (r = 0.80, r = 0.79, r = 0.79, respectively, all p < 0.001) and inversely with serum insulin levels (r = − 0.83, p < 0.001). There were no significant differences in serum GPC-4 levels among groups, and no association with GPLD1 alteration.ConclusionsSedentary diabetic rats have higher circulating GPLD1 compared to controls, which can be reversed by exercise training and is associated with modifying in glycemic and insulin profile.