Combined intervention of swimming plus metformin ameliorates the insulin resistance and impaired lipid metabolism in murine gestational diabetes mellitus

Combined intervention of swimming plus metformin ameliorates the insulin resistance and impaired lipid metabolism in murine gestational diabetes mellitus
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游泳联合二甲双胍联合干预可改善小鼠妊娠期糖尿病的胰岛素抵抗和脂质代谢受损

DOI:
10.1371/journal.pone.0195609
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发表时间:
2018-04-20
期刊:
影响因子:
3.7
通讯作者:
Chen, Keyang
Chen, Keyang
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang, Liping;Yue, Pingping;Chen, Keyang

文献摘要

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妊娠期糖尿病(GDM)对孕妇和胎儿有短期和长期的影响。游泳作为一种有氧运动,可以有效改善GDM患者的血糖水平,但单纯轻度游泳的效果不是很显著。二甲双胍作为一种口服降糖药,降糖效果明显,经济实惠,但对孕妇和胎儿的长期影响尚不完全清楚。我们推测轻度游泳与低剂量二甲双胍联合干预,可有效降低血糖,改善妊娠结局,同时避免轻度游泳用药过量和阳痿的不良反应。用链脲霉素刺激C57BL/6J小鼠发生GDM, GDM对照组(DC)血清葡萄糖、TC、TG、LDL-C明显升高,HDL-C明显降低。游泳或二甲双胍干预可轻微或中度改善GDM小鼠肝脏和骨骼肌的高血糖、胰岛素敏感性和脂质代谢,而游泳加二甲双胍联合治疗可显著改善高血糖(G10至G18组FPG较DC组降低22.2-59.5%)、胰岛素敏感性(AKT活性较DC组分别增加2.1和2.8倍)和新生脂肪生成(ACC活性分别降低3.2和7.0倍)。与DC组相比,GDM小鼠肝脏和骨骼肌中SREBP2水平分别降低1.94和5.1倍。我们得出结论,二甲双胍加游泳联合干预可能比单一干预更有效,通过改善胰岛素敏感性来改善GDM小鼠的糖脂代谢。
Gestational diabetes mellitus (GDM) has short-and long-term influence on pregnant women and fetus. Swimming, as an aerobic exercise, can effectively improve the blood glucose level in GDM, but the effect of mild swimming alone was not very substantial. Metformin, as an oral antidiabetic drug, has obvious hypoglycemic effect, and is economic also, but the long-term effect on pregnant women and fetus has not been completely clear. We hypothesize that combined intervention of mild swimming and low dose of metformin, may effectively reduce blood glucose, improve the pregnancy outcomes in GDM dams, but simultaneously avoiding the adverse effects caused by overdose of drug and impotence of mild swimming. The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, by which serum glucose, TC, TG, LDL-C were increased significantly, meanwhile HDL-C was decreased significantly in the GDM control (DC) group compared with the normal control group. Swimming or metformin intervention slightly or moderately improves hyperglycemia, insulin sensitivity and lipid metabolism both in liver and skeletal muscle from GDM mice, while combined therapy of swimming plus metformin markedly ameliorated hyperglycemia (FPG, decreased by 22.2-59.5% from G10 to G18 versus DC group), insulin sensitivity (2.1 and 2.8 fold increase, respectively, in AKT activity versus DC group) and de novo lipogenesis (3.2 and 7.0 fold decrease, respectively, in ACC activity, and 1.94 and 5.1 fold decrease, respectively, in SREBP2 level, versus DC group) both in liver and skeletal muscle from GDM mice. We conclude that the combined intervention by metformin plus swimming may be more effective than single action to ameliorate glucose and lipid metabolism via improving insulin sensitivity in GDM mice.