GLUCAGON STIMULATES INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 SECRETION IN HEALTHY-SUBJECTS, PATIENTS WITH PITUITARY INSUFFICIENCY, AND PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy in dividuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, bl ood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 c oncentrations increased significantly in response to glucagon, with ma ximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 mu g/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 mu g/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 mu g/L (P < 0.05)]. The IGFBP-1 elevation was delayed in re lation to the glucagon-induced increase in glucose and insulin concent rations. When the groups were combined, the individual IGFBP-1 peak va lue observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH -deficient patients, serum GH concentrations remained undetectable (<0 .2 mu g/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 co ncentrations in spite of increases in glucose and insulin. These resul ts suggest that glucagon is a stimulator of IGFBP-1.