Bartolome J V, Bartolome M B, Harris E B, Pauk J S, Schanberg S M
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Endocrinology. 1989 May;124(5):2153-8. doi: 10.1210/endo-124-5-2153.
Recently, our laboratory has reported that central administration of beta-endorphin to rat pups decreases hepatic and renal ornithine decarboxylase activity, a sensitive biochemical index of tissue metabolic activity. Since these organs are the major sites of insulin catabolism, it seemed possible that the plasma levels of this hormone could be altered by changes in central nervous system (CNS) beta-endorphin levels. In the current study we tested this hypothesis by administering beta-endorphin to rat pups intracisternally (ic), followed by insulin sc, and then analyzing for plasma levels of insulin and glucose at various times after the second injection. We found that the apparent biological half-life of administered insulin markedly increased in 6-day-old rats pretreated with beta-endorphin ic. Similarly, this neuropeptide prolonged the half-life of endogenous insulin, as indicated by a small but significant increase in the plasma levels of this hormone in animals given only beta-endorphin. As expected, hypoglycemia in rats injected with beta-endorphin and insulin was more pronounced than in animals given insulin alone. Naloxone administered ic reversed both actions of beta-endorphin, indicating the involvement of opioid receptors in the response. beta-Endorphin also altered insulin and glucose plasma levels in 2-, 10-, and 18-day-old rats, but there were no effects in 30-day-old animals at any of the doses used in these studies. Peripheral administration of beta-endorphin had no effect, indicating that CNS beta-endorphin's influences on insulin and glucose metabolism occur through brain-based mechanisms. The results from these studies suggest that CNS beta-endorphin may be an important modulator of insulin and glucose metabolism in preweanling rats. In as much as insulin is a major regulator of somatic growth, our findings further suggest that CNS beta-endorphin may have a major role in the control of growth during early postnatal development by influencing insulin homeostasis.
最近，我们实验室报道向幼鼠中枢注射β-内啡肽可降低肝脏和肾脏的鸟氨酸脱羧酶活性，这是组织代谢活性的一个敏感生化指标。由于这些器官是胰岛素分解代谢的主要部位，因此这种激素的血浆水平似乎有可能因中枢神经系统（CNS）β-内啡肽水平的变化而改变。在当前研究中，我们通过向幼鼠脑池内（ic）注射β-内啡肽，随后皮下注射胰岛素，然后在第二次注射后的不同时间分析胰岛素和葡萄糖的血浆水平，来检验这一假设。我们发现，在经脑池内注射β-内啡肽预处理的6日龄大鼠中，注射的胰岛素的表观生物半衰期显著延长。同样，这种神经肽延长了内源性胰岛素的半衰期，这表现为仅给予β-内啡肽的动物体内该激素的血浆水平有小幅但显著的升高。正如预期的那样，注射β-内啡肽和胰岛素的大鼠的低血糖比仅注射胰岛素的动物更明显。脑池内注射纳洛酮可逆转β-内啡肽的两种作用，表明阿片受体参与了该反应。β-内啡肽也改变了2日龄、10日龄和18日龄大鼠的胰岛素和葡萄糖血浆水平，但在这些研究中使用的任何剂量下，对30日龄动物均无影响。外周注射β-内啡肽没有作用，表明中枢神经系统β-内啡肽对胰岛素和葡萄糖代谢的影响是通过基于脑的机制发生的。这些研究结果表明，中枢神经系统β-内啡肽可能是断奶前大鼠胰岛素和葡萄糖代谢的重要调节因子。鉴于胰岛素是体细胞生长的主要调节因子，我们的研究结果进一步表明，中枢神经系统β-内啡肽可能通过影响胰岛素稳态在出生后早期发育过程中的生长控制中发挥重要作用。
