Schusdziarra V, Schick A, de la Fuente A, Specht J, Klier M, Brantl V, Pfeiffer E F
Endocrinology. 1983 Mar;112(3):885-9. doi: 10.1210/endo-112-3-885.
Opioid-active substances have been isolated from bovine beta-casein peptone (beta-casomorphin). Since the ingestion of beta-casomorphin-containing foodstuff elicits an increase in postprandial insulin release, the present study was designed to determine the effect of iv infused beta-casomorphins on insulin release. The infusion of beta-casomorphin-7, -5, -4, and -3 did not alter basal insulin secretion. During prestimulation of insulin release with amino acids and glucose the infusion of beta-casomorphin-7, -5, -4, and -3 at a dose of 1 nmol/ kg . h augmented insulin release, whereas at a concentration of 100 nmol/kg . h no further stimulatory effect was observed except for the infusion of beta-casomorphin-4. In comparison, the infusion of morphine elicited a potentiation of insulin release at the lower dose, whereas no effect was observed at the higher infusion rate. Leucine-enkephalin had no effect at the lower dose but elicited an inhibitory effect at the higher rate. The infusion of opiate-active and inactive analogs of beta-casomorphin-4 resulted in a loss of its stimulatory effect, indicating that the full tetrapeptide structure of the molecule is important for its stimulatory activity on beta-cell secretion. All stimulatory and inhibitory effects of the opioid-active substances were blocked by the specific opiate-receptor antagonist naloxone. Additionally, the present data support the concept that beta-cell secretion is stimulated by mu-receptor activation and inhibited by delta-receptor activation. The K-receptor antagonist ethyl-ketocyclazocine did not alter insulin secretion. The fact that iv administered beta-casomorphins stimulate insulin release raises the possibility that ingested food-derived opioid-active substances modulate pancreatic endocrine function also after their absorption, provided the doses employed in the present study reflect physiological concentrations of circulating beta-casomorphins.
已从牛β-酪蛋白胨中分离出阿片样活性物质（β-酪蛋白吗啡）。由于摄入含β-酪蛋白吗啡的食物会导致餐后胰岛素释放增加，本研究旨在确定静脉输注β-酪蛋白吗啡对胰岛素释放的影响。输注β-酪蛋白吗啡-7、-5、-4和-3并未改变基础胰岛素分泌。在用氨基酸和葡萄糖对胰岛素释放进行预刺激期间，以1 nmol/kg·h的剂量输注β-酪蛋白吗啡-7、-5、-4和-3可增强胰岛素释放，而在100 nmol/kg·h的浓度下，除了输注β-酪蛋白吗啡-4外，未观察到进一步的刺激作用。相比之下，输注吗啡在较低剂量时可增强胰岛素释放，而在较高输注速率下未观察到作用。亮氨酸脑啡肽在较低剂量时无作用，但在较高速率下产生抑制作用。输注β-酪蛋白吗啡-4的阿片样活性和无活性类似物导致其刺激作用丧失，表明该分子完整的四肽结构对其对β细胞分泌的刺激活性很重要。阿片样活性物质的所有刺激和抑制作用均被特异性阿片受体拮抗剂纳洛酮阻断。此外，本数据支持β细胞分泌受μ受体激活刺激而受δ受体激活抑制的概念。K受体拮抗剂乙基酮环佐辛未改变胰岛素分泌。静脉注射β-酪蛋白吗啡刺激胰岛素释放这一事实增加了以下可能性：摄入的食物源性阿片样活性物质在吸收后也会调节胰腺内分泌功能，前提是本研究中使用的剂量反映了循环中β-酪蛋白吗啡的生理浓度。
