Maternal Circulating Transthyretin Level Is Longitudinally Associated With Increased Risk of Gestational Diabetes Mellitus: It Is Not Just an Indicator of Nutritional Status

Xiong, Ting; Zhong, Chunrong; Zhou, Xian; Chen, Renjuan; Xiao, Mei; Wu, Yuanjue; Hu, Xingwen; Wang, Weiye; Li, Xiating; Liu, Chaoqun; Xiong, Guoping; Yang, Xuefeng; Hao, Liping; Yang, Nianhong

doi:10.2337/dc16-2731

Cited by 8 publications

(2 citation statements)

References 5 publications

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“…Although higher levels of TTR are usually an indicator of a better protein nutritional status [38], increased TTR has also been associated with disease, as in preeclampsia, where aggregated TTR, extruded into the maternal circulation via placental extracellular vesicles, was also reported [39]. Higher levels of TTR are also detected in diabetes type II [40,41] and gestational diabetes [38], suggesting that TTR levels must be kept in balance within healthy intervals. Too high or too low levels of TTR may contribute to the development of pathological conditions.…”

Section: Mutations In Transthyretin and Association With Diseasementioning

confidence: 99%

Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

Gião

Saavedra

Cotrina³

et al. 2020

IJMS

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Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer’s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aβ peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics.

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Section: Mutations In Transthyretin and Association With Diseasementioning

confidence: 99%

Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

Gião

Saavedra

Cotrina³

et al. 2020

IJMS

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“…Further, low serum TTR levels were shown to be associated with an increased risk of mortality in patients with dialysis [ 45 ] and acute ischemic stroke [ 46 ]. On the other hand, TTR levels have been demonstrated to be increased in the mouse model of obesity [ 47 ], type 2 diabetes [ 22 , 33 ], and in pregnant women with gestational diabetes [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

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

Alemi

Oliveira

Tavares

et al. 2021

IJMS

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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.

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Association between transthyretin concentrations and gestational diabetes mellitus in Chinese women

Liu

Chen

2020

Arch Gynecol Obstet

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Maternal Circulating Transthyretin Level Is Longitudinally Associated With Increased Risk of Gestational Diabetes Mellitus: It Is Not Just an Indicator of Nutritional Status

Cited by 8 publications

References 5 publications

Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

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

Association between transthyretin concentrations and gestational diabetes mellitus in Chinese women

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