Hydrogen Sulfide Regulates Irisin and Glucose Metabolism in Myotubes and Muscle of HFD-Fed Diabetic Mice.
Hydrogen Sulfide Regulates Irisin and Glucose Metabolism in Myotubes and Muscle of HFD-Fed Diabetic Mice.
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DOI：
10.3390/antiox11071369
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发表时间：
2022-07-14
期刊：
影响因子：
7
通讯作者：
Jain, Sushil K.
中科院分区：
文献类型：
--
作者：
Parsanathan, Rajesh;Jain, Sushil K.
虹膜蛋白是一种新的肌动因子，是由含有5个纤维连接蛋白的III型结构域(FNDC5)经蛋白水解酶裂解后由肌肉分泌的，被认为是一种新的葡萄糖稳态调节因子。胱硫醚γ裂解酶(CSE)产生硫化氢(H_2S)，参与葡萄糖的稳态。我们验证了这样的假设，即硫化氢缺乏会导致FNDC5和虹膜蛋白分泌减少，从而改变葡萄糖代谢。与正常饲料喂养的小鼠(对照组)相比，高脂饮食喂养的小鼠表现出血糖升高，CSE、H2S和PGC-1α水平显著降低，FNDC5/虹膜蛋白水平降低，肌肉氧化应激增加。高糖或棕榈酸酯可降低肌管的CSE/PGC-1、α/FNDC5水平和葡萄糖摄取。H_2S产生酶的抑制剂(丙氨酸甘氨酸和氨基氧乙酸酯)或CSE siRNA显著降低H_2S和FNDC_5的水平以及pGC-1α；类似的H_2S缺乏条件也导致葡萄糖摄取和葡萄糖摄取减少。经L半胱氨酸或硫化氢供体处理后，H_2S、PGC-1α、FNDC_5水平和葡萄糖摄取量均显著上调。成肌细胞分化表现为PGC-1α和FNDC5表达上调，这与CSE/H 2S表达上调一致。这些结果表明，H_2S水平的上调可能通过激活PGC-1α/FNDC5/虹膜蛋白信号通路而对血糖稳态产生有利的影响。
Irisin, a novel myokine, is secreted by the muscle following proteolytic cleavage of fibronectin type III domain containing 5 (FNDC5) and is considered a novel regulator of glucose homeostasis. Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H2S) and is involved in glucose homeostasis. We examined the hypothesis that H2S deficiency leads to decreased FNDC5 and irisin secretion, and thereby alters glucose metabolism. High-fat diet-fed mice exhibited elevated blood glucose and significantly reduced levels of CSE, H2S, and PGC-1α, with decreased FNDC5/irisin levels and increased oxidative stress in the muscle compared with those of normal diet-fed mice (control). High glucose or palmitate decreases CSE/PGC-1α/FNDC5 levels and glucose uptake in myotubes. Inhibitors (propargylglycine and aminooxyacetate) of H2S producing enzymes or CSE siRNA significantly decreased levels of H2S and FNDC5 along with PGC-1α; similar H2S-deficient conditions also resulted in decreased GLUT4 and glucose uptake. The levels of H2S, PGC-1α, and FNDC5 and glucose uptake were significantly upregulated after treatment with l-cysteine or an H2S donor. Myoblast differentiation showed upregulation of PGC-1α and FNDC5, which was consistent with the increased expression of CSE/H2S. These findings suggest that the upregulation of H2S levels can have beneficial effects on glucose homeostasis via activation of the PGC-1α/FNDC5/irisin signaling pathway.
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影响因子：
8.9
作者：
Matsuo, Yae;Gleitsmann, Konstanze;Mangner, Norman;Werner, Sarah;Fischer, Tina;Bowen, T. Scott;Kricke, Angela;Matsumoto, Yasuharu;Kurabayashi, Masahiko;Schuler, Gerhard;Linke, Axel;Adams, Volker
通讯作者：
Adams, Volker
影响因子：
5.1
作者：
Choi, Yeon-Kyung;Kim, Mi-Kyung;Park, Keun-Gyu
通讯作者：
Park, Keun-Gyu
影响因子：
--
作者：
Jung, Da-Woon;Ha, Hyung-Ho;Williams, Darren R.
通讯作者：
Williams, Darren R.
影响因子：
--
作者：
Giuffrè A;Vicente JB
通讯作者：
Vicente JB
影响因子：
2.1
作者：
Jain, Sushil K.;Kahlon, Gunjan;Levine, Steven N.
通讯作者：
Levine, Steven N.