Altszuler N, Winkler B, Rosenberg C R, Pi-Sunyer F X, Fuchs A R
Department of Pharmacology, New York University School of Medicine, NY 10016.
Proc Soc Exp Biol Med. 1992 Feb;199(2):236-42. doi: 10.3181/00379727-199-43353.
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.
给正常犬输注催产素（OT）可提高血浆胰岛素和胰高血糖素水平，并增加葡萄糖生成和摄取速率。本研究的目的是确定OT对葡萄糖代谢的影响是直接的还是间接的。研究在正常、未麻醉的犬身上进行，在这些犬中，OT输注叠加在生长抑素（其抑制胰岛素和胰高血糖素分泌）或可乐定（其仅抑制胰岛素分泌）的输注上。以0.2微克/千克/分钟的速率输注生长抑素可抑制血浆胰岛素和胰高血糖素的基础水平，并使OT诱导的这些激素升高幅度比单独使用OT时降低约60 - 80%。用[6 - 3H]葡萄糖测量的组织葡萄糖生成和摄取速率显著低于单独使用OT时的速率，并且葡萄糖清除率的升高被完全抑制。可乐定（30微克/千克，皮下注射）与胰岛素输注一起给予以替代基础胰岛素水平，完全阻止了OT诱导的血浆胰岛素升高，并显著降低了单独使用OT时的葡萄糖摄取，但并未降低血浆葡萄糖和胰高血糖素水平的通常升高或葡萄糖生成。为了确定OT诱导的血浆胰岛素升高是否是对血浆葡萄糖同时升高的反应，通过持续输注葡萄糖在正常犬中建立相似的血浆葡萄糖水平，并叠加OT输注。OT没有进一步提高血浆葡萄糖水平，但血浆胰岛素水平升高，表明OT可独立于血浆葡萄糖变化刺激胰岛素分泌。其他人的研究表明，将OT添加到胰岛或完整胰腺中可刺激胰岛素和胰高血糖素分泌，表明有直接作用。我们的研究与此一致，并表明在体内，OT至少部分通过对胰腺的直接作用提高血浆胰岛素水平。这些研究还表明，OT通过增加胰高血糖素分泌增加葡萄糖生成，此外，OT对葡萄糖生成可能有直接作用。OT诱导的葡萄糖摄取增加主要由胰岛素分泌增加介导。
