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Article

Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice

1
Unidad de Excelencia Instituto de Biología y Genética Molecular, University of Valladolid-CSIC, 47003 Valladolid, Spain
2
Institute for Research in Sustainable Forest Management (iuFOR), University of Valladolid, 34004 Palencia, Spain
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Institute for Memory Impairments and Neurological Disorders, University of California, Irvine (UCI MIND), Irvine, CA 92697-4545, USA
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Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Victoriano Baladrón
Cells 2021, 10(9), 2446; https://doi.org/10.3390/cells10092446
Received: 2 August 2021 / Revised: 12 September 2021 / Accepted: 15 September 2021 / Published: 16 September 2021
(This article belongs to the Special Issue Insulin-Degrading Enzyme in Health and Disease)
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. View Full-Text
Keywords: insulin-degrading enzyme; fasting; refeeding; insulin resistance; liver; metabolic adaptations; nutritional state; metabolic flexibility; lactate insulin-degrading enzyme; fasting; refeeding; insulin resistance; liver; metabolic adaptations; nutritional state; metabolic flexibility; lactate
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MDPI and ACS Style

González-Casimiro, C.M.; Cámara-Torres, P.; Merino, B.; Diez-Hermano, S.; Postigo-Casado, T.; Leissring, M.A.; Cózar-Castellano, I.; Perdomo, G. Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice. Cells 2021, 10, 2446. https://doi.org/10.3390/cells10092446

AMA Style

González-Casimiro CM, Cámara-Torres P, Merino B, Diez-Hermano S, Postigo-Casado T, Leissring MA, Cózar-Castellano I, Perdomo G. Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice. Cells. 2021; 10(9):2446. https://doi.org/10.3390/cells10092446

Chicago/Turabian Style

González-Casimiro, Carlos M., Patricia Cámara-Torres, Beatriz Merino, Sergio Diez-Hermano, Tamara Postigo-Casado, Malcolm A. Leissring, Irene Cózar-Castellano, and Germán Perdomo. 2021. "Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice" Cells 10, no. 9: 2446. https://doi.org/10.3390/cells10092446

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