Oxytocin stimulates glucagon and insulin secretion in fetal and neonatal sheep

In adults of several species arginine vasopressin (AVP) and oxytocin (OT) stimulate pancreatic secretion of immunoreactive plasma glucagon (IRG). In fetal sheep AVP is an important stress hormone and may be simultaneously secreted with OT; however, their effects on IRG secretion are not known. We sought to determine if AVP and/or OT affected pancreatic IRG secretion in fetal and neonatal sheep. Either AVP or OT was infused for 30 min in chronically catheterized fetal and neonatal sheep, obtaining peripheral arterial and/or portal venous blood samples before; 10, 15, and 30 min during; and 15, 30, and 60 min after infusion for measurements of blood gases, hematocrit, IRG, immunoreactive plasma insulin (IRI) and plasma glucose. AVP did not affect IRG or IRI in fetal sheep (mean ± SE, 133 ± 1 days gestation), but small increases occurred in portal venous blood of lambs (2–49 days old). In contrast, OT (4.6 ± 0.3 mU/min · kg; n = 12) increased fetal plasma IRG from 72 ± 5 to 86 ± 6 and 97 ± 7 pg/ml (P < 0.001) and IRI from 16 ± 2 to 20 ± 3 and 20 ± 2 μU/ml (P < 0.02) at 15 and 30 min, respectively; 157 ± 11 μU OT/min–kg had no effect. In lambs (2–49 days old), 3.0 mU OT/min–kg increased arterial (n = 15) IRG from 139 ± 19 to 367 ± 43 and 483 ± 76 pg/ml (P < 0.01) and portal IRG (n = 8) from 167 ± 39 to 341 ± 72 and 502 ± 148 pg/ml (P < 0.01), respectively. Arterial and portal IRI also rose (P < 0.01) from 36 ± 4 to 82 ± 12 and 105 ± 32 μU/ml and from 29 ± 5 to 65 ± 13 and 51 ± 7 μU/ml, respectively. Glucose was unchanged in all experiments. In fetal and neonatal sheep, AVP has minimal effects on IRG and IRI release. In contrast, OT increases both substantially; furthermore, there is a difference in fetal and neonatal responsiveness. OT may be important in modulating glucagon and insulin secretion during and after parturition.