Kwon Yeongkeun, Yoon Hanseok, Ha Jane, Lee Hyeon-Seong, Pahk Kisoo, Kwon Hyunwoo, Kim Sungeun, Park Sungsoo
Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, Republic of Korea.
Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, Republic of Korea.
Front Endocrinol (Lausanne). 2025 Mar 3;16:1460253. doi: 10.3389/fendo.2025.1460253. eCollection 2025.
Levodopa (L-3,4-dihydroxyphenylalanine)g, a dopamine precursor that circulates in the peripheral region, is involved in pancreatic glycemic control. Although previous animal studies have shown that peripheral levodopa is correlated with insulin secretion in pancreatic beta cells, the mechanism by which the pancreas uses levodopa differently in humans with obesity and type 2 diabetes remains unknown. Our study aimed to observe how the pancreas uptakes and utilizes levodopa differently under obese and diabetic conditions.
F-fluoro-L-dopa positron emission tomography-computed tomography (F-FDOPA PET-CT) was used to visualize how the human body uses levodopa under obese and diabetic conditions and presented its clinical implications. 10 patients were divided into 3 groups: 1) Group A, normal weight without type 2 diabetes; 2) Group B, obese without type 2 diabetes; and 3) Group C, obese with new-onset type 2 diabetes. All patients' lifestyle modification was conducted prior to F-FDOPA PET-CT, and plasma samples were collected to confirm changes in amino acid metabolites.
Pancreatic levodopa uptake increased in obese patients with insulin resistance, whereas it decreased in obese patients with new-onset type 2 diabetes [standardized uptake value (SUV) mean in participants with normal weight, 2.6 ± 0.7; SUV in patients with obesity, 3.6 ± 0.1; SUV in patients with obesity and new-onset type 2 diabetes, 2.6 ± 0.1, P = 0.02].
This suggested that the alterations in the functional capacity of pancreatic beta cells to take up circulating levodopa are potentially linked to the insulin resistance and the pathogenesis of type 2 diabetes. The differences in the uptake values between the groups implied that pancreatic levodopa uptake could be an early indicator of type 2 diabetes.
左旋多巴(L-3,4-二羟基苯丙氨酸)是一种在外周循环的多巴胺前体,参与胰腺血糖控制。尽管先前的动物研究表明外周左旋多巴与胰腺β细胞中的胰岛素分泌相关,但在肥胖和2型糖尿病患者中胰腺对左旋多巴的不同利用机制仍不清楚。我们的研究旨在观察在肥胖和糖尿病条件下胰腺如何不同地摄取和利用左旋多巴。
使用F-氟-L-多巴正电子发射断层扫描-计算机断层扫描(F-FDOPA PET-CT)来可视化人体在肥胖和糖尿病条件下如何使用左旋多巴,并展示其临床意义。10名患者分为3组:1)A组,体重正常且无2型糖尿病;2)B组,肥胖但无2型糖尿病;3)C组,肥胖且新发2型糖尿病。所有患者在进行F-FDOPA PET-CT之前均进行了生活方式调整,并采集血浆样本以确认氨基酸代谢物的变化。
胰岛素抵抗的肥胖患者胰腺左旋多巴摄取增加,而新发2型糖尿病的肥胖患者胰腺左旋多巴摄取减少[体重正常参与者的标准化摄取值(SUV)平均值为2.6±(0.7);肥胖患者的SUV为3.6±0.1;肥胖且新发2型糖尿病患者的SUV为2.6±0.1,P = 0.02]。
这表明胰腺β细胞摄取循环左旋多巴的功能能力改变可能与胰岛素抵抗和2型糖尿病的发病机制有关。各组摄取值的差异表明胰腺左旋多巴摄取可能是2型糖尿病的早期指标。