Pedersen Mette G B, Rittig Nikolaj, Bangshaab Maj, Berg-Hansen Kristoffer, Gopalasingam Nigopan, Gormsen Lars C, Søndergaard Esben, Møller Niels
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Medical Research Laboratory, Aarhus University, Aarhus, Denmark.
Am J Physiol Endocrinol Metab. 2024 Apr 1;326(4):E443-E453. doi: 10.1152/ajpendo.00301.2023. Epub 2024 Feb 7.
Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. In a single-blind, randomized, crossover design, eight healthy men were studied after an overnight fast on two occasions: ) during a sodium-lactate infusion (LAC) and ) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRd) were evaluated using [9,10-H]palmitate and [3-H]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [N]phenylalanine, [H]tyrosine, [N]tyrosine, and [C]urea tracers. In the postabsorptive period, plasma lactate increased to 2.7 ± 0.5 mmol/L during LAC vs. 0.6 ± 0.3 mmol/L during CTR ( < 0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared with CTR (84 ± 32 µmol/min vs. 120 ± 35 µmol/min, = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions ( = 0.7). EGP, ΔRd, and value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux ( = 0.02) and protein synthesis ( = 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole body phenylalanine flux was increased. Clinical trial registrations: NCT04710875. Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.
乳酸可能会抑制脂肪分解，从而增强胰岛素敏感性，但缺乏人体代谢方面的研究。本研究旨在确定高乳酸血症如何影响健康男性的脂肪分解、葡萄糖和蛋白质代谢以及胰岛素敏感性。在一项单盲、随机、交叉设计中，八名健康男性在两次空腹过夜后接受研究：) 在输注乳酸钠期间（LAC）和) 在输注等渗氯化钠期间（CTR）。两天均包括3小时的吸收后阶段，随后是3小时的高胰岛素-正常血糖钳夹（HEC）。使用[9,10-H]棕榈酸酯和[3-H]葡萄糖示踪剂评估脂肪分解率、内源性葡萄糖生成（EGP）和葡萄糖消失率（ΔRd）。此外，使用[N]苯丙氨酸、[H]酪氨酸、[N]酪氨酸和[C]尿素示踪剂评估全身和前臂蛋白质代谢。在吸收后阶段，LAC期间血浆乳酸水平升至2.7±0.5 mmol/L，而CTR期间为0.6±0.3 mmol/L（<0.001）。在吸收后阶段，LAC期间棕榈酸酯通量比CTR期间低30%（84±32 µmol/min对120±35 µmol/min，=0.003）。在HEC期间，两种干预措施对棕榈酸酯通量的抑制作用相似（=0.7）。LAC和CTR期间的EGP、ΔRd和值相似。在HEC期间，与CTR相比，LAC增加了全身苯丙氨酸通量（=0.02）和蛋白质合成（=0.03）；与CTR相比，LAC对前臂蛋白质代谢没有影响。在吸收后条件下，输注乳酸可使脂肪分解减少30%，但不影响葡萄糖代谢或改善胰岛素敏感性。此外，全身苯丙氨酸通量增加。临床试验注册号：NCT04710875。乳酸是一种决定性的中间代谢产物，既是能量底物又是信号分子。本研究考察了乳酸对健康男性底物代谢和胰岛素敏感性的影响。高乳酸血症可使脂肪分解减少30%，而不影响胰岛素敏感性和葡萄糖代谢。此外，高乳酸血症会增加全身氨基酸周转率。
