Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance.
Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance.
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DOI：
10.1111/jdi.12845
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发表时间：
2018-11
影响因子：
3.2
通讯作者：
Araki E
中科院分区：
文献类型：
--
作者：
Matsuba I;Matsuba R;Ishibashi S;Yamashita S;Arai H;Yokote K;Suganami H;Araki E
Pemafibrate 是一种新型选择性过氧化物酶体增殖物激活受体-α 调节剂，具有有效的降低甘油三酯和升高高密度脂蛋白胆固醇的作用。我们发现，培马贝特降低了血脂异常患者胰岛素抵抗的稳态模型评估。为了研究培马贝特如何改善胰岛素敏感性，我们使用高胰岛素正常血糖钳夹技术来确定高甘油三酯血症和胰岛素抵抗患者的内脏和外周葡萄糖摄取。总共 27 名患有高甘油三酯血症和胰岛素抵抗的患者被随机分配接受培马贝特（0.4 毫克/天，每日两次）或安慰剂治疗，为期 12 周。在第 0 周和第 12 周进行高胰岛素-正常血糖钳夹试验结合口服葡萄糖负荷，以评估内脏和外周葡萄糖摄取。 Pemafibrate（而非安慰剂）显着增加了内脏葡萄糖摄取率（分别为 19.6 ± 5.9%，P = 0.005 和 2.1 ± 7.4%，P = 0.78），但各组之间没有观察到显着差异（P = 0.084）。相反，外周葡萄糖摄取率没有显着改变。与安慰剂相比，Pemafibrate 显着降低血浆甘油三酯（−61.4 ± 16.4% vs -2.5 ± 41.4%，P = 0.001）、游离脂肪酸（−24.8 ± 23.2% vs 2.0 ± 26.8%，P = 0.016）和γ-谷氨酰转肽酶(−30 ± 46 vs 10 ± 19 U/L, P = 0.009) 水平，并且显着增加成纤维细胞生长因子 21 (457.7 ± 402.1 vs -41.7 ± 37.4 pg/mL, P = 0.007) 水平。 Pemafibrate 使高甘油三酯血症患者的内脏葡萄糖摄取量较基线增加。
Pemafibrate is a novel selective peroxisome proliferator‐activated receptor‐α modulator with potent triglyceride‐lowering and high‐density lipoprotein cholesterol‐raising effects. We showed that pemafibrate decreased the homeostatic model assessment for insulin resistance in patients with dyslipidemia. To investigate how pemafibrate improves insulin sensitivity, we used a hyperinsulinemic‐euglycemic clamp technique to determine the splanchnic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance. A total of 27 patients with hypertriglyceridemia and insulin resistance were randomly assigned to receive pemafibrate (0.4 mg/day, b.i.d.) or placebo treatment for 12 weeks. The hyperinsulinemic‐euglycemic clamp test combined with oral glucose loading was carried out at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake. Pemafibrate, but not the placebo, significantly increased the splanchnic glucose uptake rate from baseline (19.6 ± 5.9% with P = 0.005 and 2.1 ± 7.4% with P = 0.78, respectively), although no significant difference between the groups was observed (P = 0.084). Conversely, peripheral glucose uptake rate was not significantly altered. Pemafibrate, compared with the placebo, significantly decreased plasma triglycerides (−61.4 ± 16.4% vs −2.5 ± 41.4%, P = 0.001), free fatty acids (−24.8 ± 23.2% vs 2.0 ± 26.8%, P = 0.016) and gamma‐glutamyl transpeptidase (−30 ± 46 vs 10 ± 19 U/L, P = 0.009) levels, and significantly increased fibroblast growth factor 21 (457.7 ± 402.1 vs −41.7 ± 37.4 pg/mL, P = 0.007) levels. Pemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia.
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影响因子：
16.2
作者：
Cariou B;Hanf R;Lambert-Porcheron S;Zaïr Y;Sauvinet V;Noël B;Flet L;Vidal H;Staels B;Laville M
通讯作者：
Laville M
影响因子：
15.9
作者：
FERRANNINI, E;BARRETT, EJ;DEFRONZO, RA
通讯作者：
DEFRONZO, RA
影响因子：
4.8
作者：
Haluzik, M. M.;Lacinova, Z.;Haluzik, M.
通讯作者：
Haluzik, M.
影响因子：
7.1
作者：
Kliewer, Steven A.;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.
影响因子：
8.2
作者：
Bajaj, M.;Suraamornkul, S.;DeFronzo, R. A.
通讯作者：
DeFronzo, R. A.