Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology

Lin, Xuzhu; Onda, Danise Ann; Yang, Chieh Hsin; Lewis, Joshua R.; Levinger, Itamar; Loh, Kim

doi:10.1016/j.molmet.2020.101040

Cited by 24 publications

(25 citation statements)

References 162 publications

(321 reference statements)

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“…Scientific evidence confirmed that OC is involved in multiple biological processes, including energy metabolism, cognition, stress response, CV health. These physiological functions have been documented to be regulated by both OC forms, cOC and ucOC [186]. OC can bind to neurons of the hippocampus, brainstem, or midbrain, and enhance the production of monoamine neurotransmitters, prevent anxiety and depression, and support learning and memory.…”

Section: The Effect Of Vitamin K On Neurodegenerative Diseasesmentioning

confidence: 99%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

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As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.

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Section: The Effect Of Vitamin K On Neurodegenerative Diseasesmentioning

confidence: 99%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

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“…Animal and in vitro studies showed the protective effect of unOCN on vessels. This was explained by the enhanced expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production [14]. Lower serum OCN concentration was found among hypertensive men, but not women.…”

Section: Discussionmentioning

confidence: 99%

Association study between BGLAP RS1800247-polymorphic variant and type 2 diabetes mellitus development among hypertensive and non-hypertensive Ukrainians

Chumachenko

Kyrychenko²,

Ramazanova

et al. 2021

ZMJ

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The risk T2DM development depends on hereditary predisposition. According to the current data, skeleton enhances insulin gene expression in pancreatic β-cells as well as increases insulin sensitivity of adipocytes, myocytes and hepatocytes through the secretion of unOCN.The aim. To analyze the link between rs1800247 SNP and T2DM occurrence depending on the AH presence, as well as association between rs1800247 and systolic, diastolic, pulse, mean blood pressure among patients with diabetes.Materials and Methods. This study included 153 patients with diagnosed T2DM and 311 individuals without any carbohydrate metabolism disorders. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for BGLAP rs1800247-genotyping. Logistic regression with interaction term “genotype × AH” was used to estimate the association between BGLAP rs1800247-genotypes and T2DM development under dominant, recessive, over-dominant and additive models of inheritance. Linear regression was performed to investigate the influence of minor C-allele on the arterial blood pressure. All calculations were performed using Statistical Package for the Social Sciences software (SPSS, version 22.0, Chicago, IL, USA). A value of P ˂ 0,05 was considered as significant.Results. No association was found between rs1800247 single nucleotide polymorphism and T2DM development neither in AH patients, nor in subjects without AH (Paint b > 0,05). There was no impact of rs1800247 genotypes on systolic, diastolic, pulse and mean blood pressure among patients with T2DM (P > 0,05).Conclusion. It was found the lack of association between rs1800247 SNP and T2DM development as well as blood pressure parameters. Further studies with extended groups of comparison are needed for the confirmation of results. This research was a part of the scientific project “Molecular-genetic and morphological features of lower limb tissues regeneration under conditions of chronic hyperglycemia” (0117U003926).

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“…Total OC (tOC), which is a combination of circulating ucOC and cOC, is more often reported because it is easier to measure. ucOC is thought to be the bioactive form of OC, involved in the regulation of glucose homeostasis and energy metabolism ( Figure 1 ) [ [3] , [4] , [5] , [6] , [7] ]. This has led some to suggest that ucOC may be a future therapeutic target for metabolic diseases, such as insulin resistance and diabetes [ [8] , [9] , [10] ].…”

Section: Introductionmentioning

confidence: 99%

Osteocalcin and vascular function: is there a cross-talk?

Tacey

Hayes

Zulli

et al. 2021

Molecular Metabolism

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Background The bone-derived protein osteocalcin (OC), in its undercarboxylated (ucOC) form, has a beneficial effect on energy metabolism and may be a future therapeutic target for metabolic diseases. Increasing evidence suggests a link between ucOC and cardiovascular disease (CVD) development; however, the exact relationship is conflicting and unclear. Scope of review The aim of this review was to summarise the current research examining the interaction between OC and vascular dysfunction, the initiating stage in the development of atherosclerosis and CVD. Major conclusions In humans, the association between OC and vascular function is inconsistent. Several studies report that total OC (tOC) is associated with adverse function or beneficial function, whereas others report that tOC and ucOC has no effect on vascular function. The conflicting data are likely due to several methodological inconsistencies, in particular the lack of studies reporting circulating ucOC levels. In animal models, the direct administration of ucOC to isolated blood vessels ex vivo produced minimal changes in endothelial function, but importantly, no adverse responses. Finally, in human endothelial and vascular smooth muscle cells, ucOC treatment did not influence classical markers of cellular function, including endothelin-1, vascular adhesion molecule-1 and monocyte chemoattractant protein-1 after exposure to high glucose and inflammatory conditions. The lack of adverse effects in ex vivo and in vitro studies suggests that ucOC may be targeted as a future therapeutic for metabolic diseases, without the risk of detrimental effects in the vasculature. However, further studies are needed to confirm these findings and to investigate whether there is a direct beneficial influence of ucOC.

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Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology

Cited by 24 publications

References 162 publications

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

Association study between BGLAP RS1800247-polymorphic variant and type 2 diabetes mellitus development among hypertensive and non-hypertensive Ukrainians

Osteocalcin and vascular function: is there a cross-talk?

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