Enhancement of the GH responsiveness to GH releasing stimuli by lysine vasopressin in type 1 diabetic subjects.

Abstract

We tested the possibility that lysine vasopressin (LVP) changes the GH responsiveness to exogenously administered GH-RH (at its minimal and maximal doses), clonidine (which is thought to stimulate endogenous GH-RH release) and arginine (which is thought to inhibit somatostatin) in patients with type 1 diabetes mellitus and normal subjects. Normal male subjects (NC) and age- and weight-matched insulin-dependent diabetic men (DM) with good metabolic control were studied. An iv bolus of LVP at a dose (15 microg/kg body weight (BW)) lower than the minimal GH releasing effective dose was injected just before the I.V. injection of the minimal effective dose of GH-RH (0.035 microg/kg BW) in 10 NC and 10 DM, the I.V. injection of the maximal effective dose of GH-RH (100 microg) in 7 NC and 7 DM, the I.V. infusion of arginine (30 g over 30 min) in 7 NC and 8 DM or the oral administration of clonidine (150 microg) in 7 NC and 8 DM. On different occasions, GH stimuli, LVP or normal saline were given alone to the same normal and diabetic subjects. GH responses in the presence and absence of LVP were measured and compared within each group and between normal and diabetic groups. LVP or normal saline administration did not modify the basal concentrations of GH in any subject. The administration of GH-RH (at the minimal dose), arginine or clonidine alone induced significantly higher GH responses in the diabetic subjects than in the normal controls. At the maximal dose GH-RH induced similar GH responses in normal and diabetic subjects. The simultaneous administration of LVP did not change the GH response to any challenging stimulation in the normal controls; in contrast, GH-RH- (at both minimal and maximal dose), arginine- and clonidine-induced GH increments were significantly enhanced by LVP in the diabetic subjects. These data show that in diabetic, but not in normal subjects LVP enhances the GH responsiveness to secretagogues, such as GH-RH, clonidine and arginine, which act through three different mechanisms. These findings suggest that in diabetes mellitus, vasopressin functions as a primer for various GH responses.