Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver

Abstract

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 TTR 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.

Association between rat decompression sickness resistance, transthyretin single nucleotide polymorphism, and expression: A pilot study

“…Interestingly, a large genotypic and phenotypic analysis conducted in humans showed an association between low TTR hepatic expression and lower body height (Pathak et al., 2022 ). Increased TTR expression also increases mitochondrial density whereas its insufficiency triggers a higher degree of oxidative phosphorylation in the liver (Alemi et al., 2021 ). The lower amount of TTR mRNAs in the liver of DCS‐resistant rats would therefore be coherent with the decrease in body weight observed in DCS‐resistant rats throughout the selection process (Lautridou, Buzzacott, et al., 2017 ), as well as with the hormonal and energetic remodeling (Vallée et al., 2021 ) and the lower basal mitochondrial oxygen consumption due to lower mitochondrial volume in skeletal muscle (Lautridou et al., 2020 ) that we previously reported in DCS‐resistance animals.…”

Applying Network Pharmacology and Molecular Docking in the Screening for Molecular Mechanisms of Ampalaya (Momordica charantia L.) and Banaba (Lagerstroemia speciosa L.) against Type 2 Diabetes Mellitus

“…Transthyretin works by influencing the secretion of insulin and glucagon. 47 , 48 Moreover, it stabilizes the retinol-binding protein 4 (RBP4) at a higher steady-state concentration in circulation which eventually lead to insulin resistance. However, Jayaweera and colleagues showed that transthyretin can slow down the formation of islet amyloid polypeptide (IAPP).…”

Serum prealbümin konsantrasyonları albümin, kalsiyum, magnezyum ve fosfor düzeyleri ile ilişkili olabilir mi?

“…Although most of it is synthesised in hepatocytes, a very small amount originates from tissues such as pancreas. 1 This protein is also known and named as transthyretin because of its thyroid hormones and vitamin A binding properties. 2 Prealbumin is a specific and sensitive marker of nutritional conditions.…”