Combined treatment of dipeptidyl peptidase‐4 inhibitor and exercise training improves lipid profile in KK/Ta mice
Combined treatment of dipeptidyl peptidase‐4 inhibitor and exercise training improves lipid profile in KK/Ta mice
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二肽基肽酶 4 抑制剂和运动训练联合治疗可改善 KK/Ta 小鼠的血脂状况
DOI：
10.1113/ep087449
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发表时间：
2019
影响因子：
2.7
通讯作者：
Naito Yuji
中科院分区：
文献类型：
--
作者：
Tanimura Yuko;Aoi Wataru;Mizushima Katsura;Higashimura Yasuki;Naito Yuji
新发现这项研究的中心问题是什么？对接受胰岛素治疗的2型糖尿病患者来说，运动会带来低血糖的风险。二肽基肽酶-4(DPP-4)抑制剂与运动相结合可以有效，因为它们减少了低血糖的发生率。我们评估了这种联合治疗对糖尿病KK/Ta小鼠肝脏脂质代谢的影响。主要发现和它的重要性是什么？DPP-4抑制剂和运动的结合降低了低血糖的风险，通过抑制过量的胰岛素分泌和减少肝脏脂肪堆积，有效地改善了胰岛素抵抗，CD36的下调得到了验证。摘要运动训练在预防糖尿病和/或血脂异常方面的作用已经确定。二肽基肽酶-4(DPP-4)抑制剂可改善胰岛素敏感性，作为治疗肝脂积聚的药物已引起人们的关注。DPP-4抑制剂与运动训练联合应用对防治肝脂积聚的作用尚不清楚。在这里，我们研究了DPP-4抑制剂alogliptin是否增强了运动诱导的糖尿病小鼠肝脏脂质堆积的预防效果。以高脂饲料喂养BALB/c和KK/Ta小鼠。将小鼠分为5组：B组：BALB/c小鼠；K，KK/Ta组；K-A，KK/Ta组(0.01%)；K-Ex，KK/Ta组，运动训练(每周−1，15~20min，−1，30min)；K-Ex+A，KK/Ta组，每组8只或9只。8周后，K-Ex+A组血糖、胰岛素、甘油三酯水平及肝脏甘油三酯水平均显著低于K组。K组大鼠肝脏PPAR-γ表达水平显著高于其他组。此外，K-Ex+A和B组大鼠肝脏CD36表达水平明显低于K组。因此，DPP-4抑制剂与运动训练的联合治疗对高脂饮食诱导的KK/Ta小鼠的肝脂积聚是有效的。这项研究的结果为安全运动疗法的实践提供了有用的支持，即使在需要DPP-4抑制剂治疗的糖尿病患者中也是如此。
New FindingsWhat is the central question of this study?Exercise for type 2 diabetes patients treated with insulin therapy involves the risk of hypoglycaemia. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors can be effective in combination with exercise because they reduce the incidence of hypoglycaemia. We evaluated the effect of this combination of treatments on hepatic lipid metabolism in diabetic KK/Ta mice.What is the main finding and its importance?The combination of a DPP‐4 inhibitor and exercise, which lowers the risk of hypoglycaemia, is useful for improving insulin resistance by inhibiting excess insulin secretion and decreasing hepatic lipid accumulation, validated by downregulated CD36.AbstractThe role of exercise training in prevention of diabetes and/or dyslipidaemia has been firmly established. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors improve insulin sensitivity and have attracted attention as therapeutics for hepatic lipid accumulation. The effect of a combination of DPP‐4 inhibitor and exercise training on the prevention and treatment of hepatic lipid accumulation is unclear. Here, we investigated whether alogliptin, a DPP‐4 inhibitor, enhances the preventive effect of exercise‐induced hepatic lipid accumulation in diabetic mice. Balb/c and KK/Ta mice were fed a high‐fat diet. Mice were divided into the following five groups: B, Balb/c mice; K, KK/Ta mice; K‐A, KK/Ta mice with alogliptin (0.01%); K‐Ex, KK/Ta mice with exercise training (3 days week−1, 15–20 m min−1for 30 min); and K‐Ex+A, KK/Ta mice with alogliptin and exercise training (n= 8 or 9 mice per group). After 8 weeks, glucose, insulin and triglyceride concentrations in the blood and triglyceride levels in the liver were significantly lower in the K‐Ex+A group than in the K group. The liver expression level of PPAR‐γ in the K group was significantly higher than that in the other groups. Additionally, the liver CD36 expression level was significantly lower in the K‐Ex+A and B groups than in the K group. Thus, combined therapy of a DPP‐4 inhibitor with exercise training was effective against high‐fat diet‐induced hepatic lipid accumulation in KK/Ta mice. The results of this study provide useful support for the practice of safe exercise therapy even in diabetic patients who require treatment with a DPP‐4 inhibitor.
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DOI：
10.12659/msm.890989
发表时间：
2014-09-17
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Kanazawa I;Tanaka K;Sugimoto T
通讯作者：
Sugimoto T
影响因子：
8.2
作者：
Cassidy S;Thoma C;Hallsworth K;Parikh J;Hollingsworth KG;Taylor R;Jakovljevic DG;Trenell MI
通讯作者：
Trenell MI
影响因子：
15.9
作者：
Okuno, A;Tamemoto, H;Kadowaki, T
通讯作者：
Kadowaki, T
吡格列酮对2型糖尿病患者腹部脂肪分布及胰岛素敏感性的影响
DOI：
10.1210/jcem.87.6.8567
发表时间：
2002
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Miyazaki,Yoshinori;Mahankali,Archana;Matsuda,Masafumi;Mahankali,Srikanth;Hardies,Jean;Cusi,Kenneth;Mandarino,LawrenceJ;DeFronzo,RalphA
通讯作者：
DeFronzo,RalphA
DOI：
10.1016/j.bbrc.2005.08.070
发表时间：
2005-10-14
影响因子：
3.1
作者：
Inoue, M;Ohtake, T;Okumura, T
通讯作者：
Okumura, T