Attenuated suppression of lipolysis explains the increases in triglyceride secretion and concentration associated with basal insulin peglispro relative to insulin glargine treatment in patients with type 1 diabetes.
相对于甘精胰岛素治疗 1 型糖尿病患者,减弱的脂肪分解抑制解释了与基础胰岛素 peglispro 相关的甘油三酯分泌和浓度的增加。
basal insulin drug mechanism phase I-II study type 1 diabetes
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摘要

AIMS:To test the hypothesis that, as well as lowering weight and increasing plasma triglyceride (TG) levels and hepatic fat compared with insulin glargine (GL) in patients with type 1 diabetes, the attenuated peripheral effects of basal insulin peglispro (BIL) may include increased free fatty acid flux to the liver, causing increased very-low-density lipoprotein (VLDL)-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition.
METHODS:In this open-label, randomized, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualized, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10-3 H]palmitate infusion. VLDL-TG secretion, clearance and oxidation rate were assessed using primed-constant infusion of ex vivo labelled [1-14 C]VLDL-TG, while VLDL-TG storage rate was assessed using [9,10-3 H]VLDL-TG bolus injection.
RESULTS:The VLDL-TG concentration and secretion rate, and palmitate flux were statistically significantly higher during BIL than during GL treatment (58%, 51% and 35%, respectively). The ratios of least squares (LS) geometric means for VLDL-TG clearance and oxidation were 0.92 (95% confidence interval [CI] 0.72, 1.17) and 1.31 (95% CI 0.91, 1.90), respectively. The difference in LS means for VLDL-TG storage rate was -0.36 (95% CI -0.83, 0.12).
CONCLUSIONS:BIL-treated patients had higher effective lipolysis, VLDL-TG secretion and VLDL-TG concentration compared with GL-treated patients, explaining the increased plasma TG concentrations reported previously. Data support attenuated effects of BIL on lipolysis, in addition to the recently described hepato-preferential glucodynamic effects.

译文

目的: 为了验证这一假设,与甘精胰岛素 (GL) 相比,在 1 型糖尿病患者中,除了降低体重和增加血浆甘油三酯 (TG) 水平以及肝脏脂肪, 基础胰岛素 peglispro (BIL) 减弱的周边效应可能包括增加肝脏的游离脂肪酸流量,引起极低密度脂蛋白 (VLDL)-甘油三酯分泌和脂质氧化增加,甘油三酯脂肪组织沉积减少。
方法: 在这项开放标签、随机、 2 期交叉研究中,14 名 1 型糖尿病患者接受了为期 3 周的每日一次、个性化、稳定的 BIL 或 GL 剂量。棕榈酸盐流量使用 [9,10-3 H] 棕榈酸盐输注进行评估。VLDL-TG 的分泌、清除和氧化率是通过使用体外标记的 [1-14 C] VLDL-TG 的启动恒定输注来评估的, 而 VLDL-TG 储存率是使用 [9,10-3 H] VLDL-TG 推注来评估的。
结果: VLDL-TG 浓度和分泌率以及棕榈酸酯流量在 BIL 期间显著高于 GL 期间 (分别为 58%,51% 和 35%)。VLDL-TG 清除和氧化的最小二乘 (LS) 几何平均值的比率分别为 0.92 (95% 置信区间 [CI] 0.72,1.17) 和 1.31 (95% CI 0.91,1.90)。VLDL-TG 存储速率的 LS 平均值差异为-0.36 (95% CI-0.83,0.12)。
结论: 与 GL 治疗的患者相比,BIL 治疗的患者有更高的有效脂肪分解、 VLDL-TG 分泌和 VLDL-TG 浓度,这解释了之前报道的血浆 TG 浓度的增加。数据支持 BIL 对脂肪分解的衰减作用,以及最近描述的肝优先糖动力学效应。

Lipolysis

内分泌 代谢 临床研究术语
概述  :  

脂解是代谢途径,通过该脂质的甘油三酯被水解成甘油和三个脂肪酸。在禁食或运动期间它被用来调动储存的能量,通常发生在脂肪细胞中。脂肪分解是由几种激素引起的,包括胰高血糖素,肾上腺素,去甲肾上腺素,生长激素,心钠素,脑钠素和皮质醇。 病理机制 在这些区域,细胞内甘油三酸酯储存在细胞质脂质小滴中。当脂肪酶被磷酸化,通过水解的多个步骤,击穿甘油三酯分解为脂肪酸和甘油的脂滴。水解的每个步骤导致一种脂肪酸的去除。脂肪分解的第一步和限速步骤是

lipolysis   英 /lɪ'pɒlɪsɪs/

释    义   n. 脂类分解;[生化] 脂解作用

例    句   The treatment is a form ofnon-invasive, laser-assisted fat-removal, or lipolysis.这是一种非侵入性、激光辅助消除脂肪或分解脂类的疗法。

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