Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver
Transthyretin (TTR), a 55 kDa evolutionarily conserved protein, presents altered levels in several conditions, including malnutrition, inflammation, diabetes, and Alzheimer’s Disease. It has been shown that TTR is involved in several functions, such as insulin release from pancreatic β-cells, recove...
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doaj-c8389df492e6457191261400aee118022021-06-30T23:19:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226073607310.3390/ijms22116073Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the LiverMobina Alemi0Ângela Oliveira1Sofia C. Tavares2José Ricardo Vieira3Marco G. Alves4Pedro F. Oliveira5Isabel Cardoso6i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalUnit for Multidisciplinary Research in Biomedicine (UMIB), Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, PortugalQOPNA & LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugali3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalTransthyretin (TTR), a 55 kDa evolutionarily conserved protein, presents altered levels in several conditions, including malnutrition, inflammation, diabetes, and Alzheimer’s Disease. It has been shown that TTR is involved in several functions, such as insulin release from pancreatic β-cells, recovery of blood glucose and glucagon levels of the islets of Langerhans, food intake, and body weight. Here, the role of TTR in hepatic glucose metabolism was explored by studying the levels of glucose in mice with different TTR genetic backgrounds, namely with two copies of the <i>TTR</i> gene, TTR+/+; with only one copy, TTR+/−; and without TTR, TTR−/−. Results showed that TTR haploinsufficiency (TTR+/−) leads to higher glucose in both plasma and in primary hepatocyte culture media and lower expression of the influx glucose transporters, GLUT1, GLUT3, and GLUT4. Further, we showed that TTR haploinsufficiency decreases pyruvate kinase M type (PKM) levels in mice livers, by qRT-PCR, but it does not affect the hepatic production of the studied metabolites, as determined by 1H NMR. Finally, we demonstrated that TTR increases mitochondrial density in HepG2 cells and that TTR insufficiency triggers a higher degree of oxidative phosphorylation in the liver. Altogether, these results indicate that TTR contributes to the homeostasis of glucose by regulating the levels of glucose transporters and PKM enzyme and by protecting against mitochondrial oxidative stress.https://www.mdpi.com/1422-0067/22/11/6073transthyretinglucose metabolismglucose transporterslivermitochondria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mobina Alemi Ângela Oliveira Sofia C. Tavares José Ricardo Vieira Marco G. Alves Pedro F. Oliveira Isabel Cardoso |
spellingShingle |
Mobina Alemi Ângela Oliveira Sofia C. Tavares José Ricardo Vieira Marco G. Alves Pedro F. Oliveira Isabel Cardoso Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver International Journal of Molecular Sciences transthyretin glucose metabolism glucose transporters liver mitochondria |
author_facet |
Mobina Alemi Ângela Oliveira Sofia C. Tavares José Ricardo Vieira Marco G. Alves Pedro F. Oliveira Isabel Cardoso |
author_sort |
Mobina Alemi |
title |
Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver |
title_short |
Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver |
title_full |
Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver |
title_fullStr |
Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver |
title_full_unstemmed |
Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver |
title_sort |
exploring the physiological role of transthyretin in glucose metabolism in the liver |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
Transthyretin (TTR), a 55 kDa evolutionarily conserved protein, presents altered levels in several conditions, including malnutrition, inflammation, diabetes, and Alzheimer’s Disease. It has been shown that TTR is involved in several functions, such as insulin release from pancreatic β-cells, recovery of blood glucose and glucagon levels of the islets of Langerhans, food intake, and body weight. Here, the role of TTR in hepatic glucose metabolism was explored by studying the levels of glucose in mice with different TTR genetic backgrounds, namely with two copies of the <i>TTR</i> gene, TTR+/+; with only one copy, TTR+/−; and without TTR, TTR−/−. Results showed that TTR haploinsufficiency (TTR+/−) leads to higher glucose in both plasma and in primary hepatocyte culture media and lower expression of the influx glucose transporters, GLUT1, GLUT3, and GLUT4. Further, we showed that TTR haploinsufficiency decreases pyruvate kinase M type (PKM) levels in mice livers, by qRT-PCR, but it does not affect the hepatic production of the studied metabolites, as determined by 1H NMR. Finally, we demonstrated that TTR increases mitochondrial density in HepG2 cells and that TTR insufficiency triggers a higher degree of oxidative phosphorylation in the liver. Altogether, these results indicate that TTR contributes to the homeostasis of glucose by regulating the levels of glucose transporters and PKM enzyme and by protecting against mitochondrial oxidative stress. |
topic |
transthyretin glucose metabolism glucose transporters liver mitochondria |
url |
https://www.mdpi.com/1422-0067/22/11/6073 |
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