The circulating IGF system and its relationship with 24-h glucose regulation and insulin sensitivity in healthy subjects

Objective and Design It has been suggested that circulating free IGF-I participates in glucose homeostasis and that IGFBP-1 reflects changes in insulin sensitivity. To study this further, we examined 10 healthy, nonobese subjects under standardized conditions for 24 h with and without an intravenous infusion of glucose, the latter in order to augment insulin sensitivity. Serum was collected every 2 h for analysis of free and total IGFs, IGFBP-1, -2 and -3 and the acid labile subunit (ALS). Insulin sensitivity was estimated at the end of each 24-h study period by use of the hyperinsulinaemic euglycaemic clamp technique. Results Glucose infusion resulted in mild hyperglycaemia (P<0.0001), a reduction in IGFBP-1 by approximately 40% (P<0.0003), and increased insulin and C-peptide levels (P<0.0001). Glucose infusion also increased insulin sensitivity (P<0.003). However, despite the reduction in IGFBP-1, glucose infusion did not increase free IGF-I over the control level, and free IGF-II was slightly reduced (P<0.02). Irrespective of glucose infusion, free IGF-I and -II remained stable during daytime (i.e. they were unresponsive to meal-related changes in plasma glucose), but both free fractions decreased during the night, reaching nadir at 04.00 h. None of the other members of the IGF system showed any relationship with plasma glucose levels. Finally, we failed to observe any relationship between changes in insulin sensitivity and the circulating IGF system. Conclusion We found no evidence that the circulating IGF system is involved in meal-related blood glucose regulation or that it reflects short-term changes in insulin sensitivity in healthy, nonobese subjects. However, we cannot preclude that the observed changes in circulating IGFBP-1 may affect the glucose-lowering effect of IGF-I and -II at the local tissue level.