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miR-27b Modulates Insulin Signaling in Hepatocytes by Regulating Insulin Receptor Expression

Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain
Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA
IMDEA Research Institute of Food and Health Sciences, 28049 Madrid, Spain
Fundación Biofisika Bizkaia, 48940 Leioa, Spain
Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Spain
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8675;
Received: 21 October 2020 / Revised: 14 November 2020 / Accepted: 16 November 2020 / Published: 17 November 2020
(This article belongs to the Special Issue Progress in Glucose Metabolism)
Insulin resistance (IR) is one of the key contributing factors in the development of type 2 diabetes mellitus (T2DM). However, the molecular mechanisms leading to IR are still unclear. The implication of microRNAs (miRNAs) in the pathophysiology of multiple cardiometabolic pathologies, including obesity, atherosclerotic heart failure and IR, has emerged as a major focus of interest in recent years. Indeed, upregulation of several miRNAs has been associated with obesity and IR. Among them, miR-27b is overexpressed in the liver in patients with obesity, but its role in IR has not yet been thoroughly explored. In this study, we investigated the role of miR-27b in regulating insulin signaling in hepatocytes, both in vitro and in vivo. Therefore, assessment of the impact of miR-27b on insulin resistance through the hepatic tissue is of special importance due to the high expression of miR-27b in the liver together with its known role in regulating lipid metabolism. Notably, we found that miR-27b controls post-transcriptional expression of numerous components of the insulin signaling pathway including the insulin receptor (INSR) and insulin receptor substrate 1 (IRS1) in human hepatoma cells. These results were further confirmed in vivo showing that overexpression and inhibition of hepatic miR-27 enhances and suppresses hepatic INSR expression and insulin sensitivity, respectively. This study identified a novel role for miR-27 in regulating insulin signaling, and this finding suggests that elevated miR-27 levels may contribute to early development of hepatic insulin resistance. View Full-Text
Keywords: microRNA; type 2 diabetes mellitus; miR-27b; insulin signaling; INRS microRNA; type 2 diabetes mellitus; miR-27b; insulin signaling; INRS
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MDPI and ACS Style

Benito-Vicente, A.; Uribe, K.B.; Rotllan, N.; Ramírez, C.M.; Jebari-Benslaiman, S.; Goedeke, L.; Canfrán-Duque, A.; Galicia-García, U.; Saenz De Urturi, D.; Aspichueta, P.; Suárez, Y.; Fernández-Hernando, C.; Martín, C. miR-27b Modulates Insulin Signaling in Hepatocytes by Regulating Insulin Receptor Expression. Int. J. Mol. Sci. 2020, 21, 8675.

AMA Style

Benito-Vicente A, Uribe KB, Rotllan N, Ramírez CM, Jebari-Benslaiman S, Goedeke L, Canfrán-Duque A, Galicia-García U, Saenz De Urturi D, Aspichueta P, Suárez Y, Fernández-Hernando C, Martín C. miR-27b Modulates Insulin Signaling in Hepatocytes by Regulating Insulin Receptor Expression. International Journal of Molecular Sciences. 2020; 21(22):8675.

Chicago/Turabian Style

Benito-Vicente, Asier, Kepa B. Uribe, Noemi Rotllan, Cristina M. Ramírez, Shifa Jebari-Benslaiman, Leigh Goedeke, Alberto Canfrán-Duque, Unai Galicia-García, Diego Saenz De Urturi, Patricia Aspichueta, Yajaira Suárez, Carlos Fernández-Hernando, and Cesar Martín. 2020. "miR-27b Modulates Insulin Signaling in Hepatocytes by Regulating Insulin Receptor Expression" International Journal of Molecular Sciences 21, no. 22: 8675.

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