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Effects of a novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate (K-877), 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 (K-877), on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance.
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Matsuba I, Matsuba R, Ishibashi S, Yamashita S, Arai H, Yokote K, Suganami H, Araki E,


Matsuba I, Matsuba R, Ishibashi S, Yamashita S, Arai H, Yokote K, Suganami H, Araki E, (click to view)

Matsuba I, Matsuba R, Ishibashi S, Yamashita S, Arai H, Yokote K, Suganami H, Araki E,

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Journal of diabetes investigation 2018 03 30() doi 10.1111/jdi.12845
Abstract
AIMS/INTRODUCTION
Pemafibrate (K-877) is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) with potent triglyceride (TG)-lowering and high-density lipoprotein cholesterol-raising effects. We showed that pemafibrate decreased the homeostasis model assessment for insulin resistance (HOMA-IR) 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.

MATERIALS AND METHODS
A total of 27 patients with hypertriglyceridemia and insulin resistance were randomly assigned to receive pemafibrate (0.4 mg/day, twice daily) or placebo treatment for 12 weeks. The hyperinsulinemic-euglycemic clamp test combined with oral glucose loading was performed at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake.

RESULTS
Pemafibrate, but not 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 placebo, significantly decreased plasma TGs (-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 (FGF21) (457.7±402.1 vs. -41.7±37.4 pg/ml, p=0.007) levels.

CONCLUSIONS
Pemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia. This article is protected by copyright. All rights reserved.

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