Rehfeld Jens F
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
J Intern Med. 2025 Sep;298(3):251-267. doi: 10.1111/joim.20110. Epub 2025 Jun 25.
Cholecystokinin (CCK) is a classic gut hormone that has been known for almost a century to regulate gallbladder emptying, pancreatic enzyme secretion, and gastrointestinal motor activity. In 1968, the CCK structure was identified by Viktor Mutt and Erik Jorpes from porcine gut extracts as a peptide of 33 amino acid residues. Based on that structure, physiological, immunochemical, molecular, and cell biological research has since expanded the insight into the biology of CCK remarkably. Thus, CCK was the first identified intestinal satiety signal to the brain. Moreover, the CCK gene is now known to be expressed in different molecular forms not only in the gut, but very much so in central and peripheral neurons, in addition to extra-intestinal endocrine cells, immune cells, cardiomyocytes, spermatogenic cells, and certain fat cells. Accordingly, CCK peptides function not only as hormones. They are also neurotransmitters, paracrine growth and satiation factors, anti-inflammatory cytokines, incretins, adipokins, myokines, potential fertility factors, and tumor markers. Consequently, CCK biology has now opened windows for insights into pathophysiology with diagnostic and therapeutic possibilities in metabolic disorders (obesity, eating disorders, and diabetes mellitus), gallbladder disease, neuropsychiatric diseases (cerebral tumors, memory, and anxiety disorders), cardiac diseases (prognosis in heart failure), neuroendocrine and pediatric tumors, as well as perhaps infertility.
胆囊收缩素(CCK)是一种经典的肠道激素,近一个世纪以来一直被认为可调节胆囊排空、胰腺酶分泌和胃肠运动活动。1968年,维克托·穆特(Viktor Mutt)和埃里克·约佩斯(Erik Jorpes)从猪肠道提取物中鉴定出CCK的结构,它是一种由33个氨基酸残基组成的肽。基于该结构,生理、免疫化学、分子和细胞生物学研究极大地拓展了对CCK生物学特性的认识。因此,CCK是首个被发现的向大脑传递饱腹感的肠道信号。此外,现在已知CCK基因不仅在肠道中以不同的分子形式表达,在中枢和外周神经元中表达也非常多,此外还在肠外内分泌细胞、免疫细胞、心肌细胞、生精细胞和某些脂肪细胞中表达。相应地,CCK肽不仅作为激素发挥作用。它们还是神经递质、旁分泌生长和饱腹感因子、抗炎细胞因子、肠促胰岛素、脂肪因子、肌动蛋白、潜在的生育因子和肿瘤标志物。因此,CCK生物学现在为深入了解病理生理学打开了窗口,在代谢紊乱(肥胖、饮食失调和糖尿病)、胆囊疾病、神经精神疾病(脑肿瘤、记忆和焦虑症)、心脏病(心力衰竭的预后)、神经内分泌和儿科肿瘤以及可能的不孕症方面具有诊断和治疗潜力。