Spontaneous, high frequency insulin oscillations are easily entrainable to exogenous glucose in vitro and in vivo, but this property is lost in type 2 diabetes. We hypothesized that this lack of entrainment in type 2 diabetes would be specific to glucose. This was tested in nine control and ten type 2 diabetic subjects. Serial blood sampling at one min intervals was carried out for 60 minutes in the basal state and for 120 min while small (1-60 mg/kg) boluses of arginine were injected intravenously at exact 29 minute intervals. Samples were analyzed for insulin concentrations and time series analysis was carried out using spectral analysis. In control subjects, the mean period of basal plasma insulin oscillations was 10.3 ± 1.3 min, and was entrained by arginine to a mean period of 14.9 ± 0.6 min (p<0.00001 vs basal). Similarly, in diabetic subjects, spontaneous insulin oscillations were entrained by arginine; mean basal insulin period was 10.0 ± 1.0 min and 14.5 ± 1.8 min with arginine boluses (p<0.00001). All of the primary peaks observed in spectral analysis were statistically significant (p<0.05). Percent of total power of primary peaks ranged from 17-68%. Thus, arginine boluses entrain spontaneous high frequency insulin oscillations in diabetic subjects. This represents a distinct and striking difference from the resistance of the beta cell to glucose entrainment in diabetes. We conclude that loss of entrainment of spontaneous high frequency insulin oscillations in diabetes is likely a glucose-specific manifestation of beta cell secretory dysfunction.