Regulation of insulin and glucose plasma levels by central nervous system beta-endorphin in preweanling rats.

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.