Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice.
Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice.
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DOI：
10.3390/cells10092446
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发表时间：
2021-09-16
期刊：
影响因子：
6
通讯作者：
Perdomo G
中科院分区：
文献类型：
--
作者：
González-Casimiro CM;Cámara-Torres P;Merino B;Diez-Hermano S;Postigo-Casado T;Leissring MA;Cózar-Castellano I;Perdomo G
胰岛素降解酶（IDE）是一种高度保守和广泛表达的锌金属肽酶，可调节肝脏胰岛素敏感性，但其对空腹至餐后过渡的调节作用尚不清楚。在这项工作中，我们研究了IDE mRNA和蛋白水平的调节，以及其蛋白水解活性在肝脏，骨骼肌和肾脏禁食（18小时）和再喂养（30分钟和3小时）的条件下，在小鼠喂养标准（SD）或高脂肪（HFD）饮食。在喂食HFD的小鼠的肝脏中，禁食降低了IDE蛋白水平（约30%）;而在喂食SD和HFD的小鼠中，再喂食增加了其活性（约45%）。同样，在禁食状态下喂食HFD的小鼠骨骼肌中IDE蛋白水平降低（约30%）。循环乳酸浓度与肝脏IDE活性和蛋白水平直接相关。值得注意的是，肝裂解物中的L-乳酸盐以剂量依赖性方式增强IDE活性。此外，肝脏和肌肉组织中的IDE蛋白水平，而不是其活性，与胰岛素抵抗的替代标志物（HOMA指数）呈负相关（R2分别为0.3734和0.2951; p < 0.01）。最后，多变量分析表明，循环胰岛素，葡萄糖，非酯化脂肪酸和乳酸水平可能是重要的调节IDE在肝脏和肌肉组织。我们的研究结果强调，IDE在肝脏和骨骼肌的营养调节比以前预期的小鼠更复杂，禁食/再喂养不会强烈影响肾脏IDE的调节。
Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed Zn2+-metallopeptidase that regulates hepatic insulin sensitivity, albeit its regulation in response to the fasting-to-postprandial transition is poorly understood. In this work, we studied the regulation of IDE mRNA and protein levels as well as its proteolytic activity in the liver, skeletal muscle, and kidneys under fasting (18 h) and refeeding (30 min and 3 h) conditions, in mice fed a standard (SD) or high-fat (HFD) diets. In the liver of mice fed an HFD, fasting reduced IDE protein levels (~30%); whereas refeeding increased its activity (~45%) in both mice fed an SD and HFD. Likewise, IDE protein levels were reduced in the skeletal muscle (~30%) of mice fed an HFD during the fasting state. Circulating lactate concentrations directly correlated with hepatic IDE activity and protein levels. Of note, L-lactate in liver lysates augmented IDE activity in a dose-dependent manner. Additionally, IDE protein levels in liver and muscle tissues, but not its activity, inversely correlated (R2 = 0.3734 and 0.2951, respectively; p < 0.01) with a surrogate marker of insulin resistance (HOMA index). Finally, a multivariate analysis suggests that circulating insulin, glucose, non-esterified fatty acids, and lactate levels might be important in regulating IDE in liver and muscle tissues. Our results highlight that the nutritional regulation of IDE in liver and skeletal muscle is more complex than previously expected in mice, and that fasting/refeeding does not strongly influence the regulation of renal IDE.
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影响因子：
7.7
作者：
Kelley, DE;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
5.8
作者：
Fosam, Andin;Sikder, Shanaz;Muniyappa, Ranganath
通讯作者：
Muniyappa, Ranganath
影响因子：
--
作者：
CONSOLI, A;NURJHAN, N;GERICH, JE
通讯作者：
GERICH, JE
影响因子：
15.9
作者：
KELLEY, DE;MOKAN, M;MANDARINO, LJ
通讯作者：
MANDARINO, LJ
DOI：
10.1002/oby.23161
发表时间：
2021-06
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Brown JC;Carson TL;Thompson HJ;Agurs-Collins T
通讯作者：
Agurs-Collins T