Role of insulin and glucagon in oxytocin effects on glucose metabolism.
Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.
Department of Pharmacology, New York University School of Medicine, NY 10016.
N
N
Altszuler
B
B
Winkler
C R
CR
Rosenberg
F X
FX
Pi-Sunyer
A R
AR
Fuchs
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003000:Clonidine; D004285:Dogs; D005934:Glucagon / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D013004:Somatostatin
D001786:Blood Glucose; D007328:Insulin; D010121:Oxytocin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose; D003000:Clonidine