Osteocalcin and the Regulation of Glucose Metabolism

Vella, Adrian; Kumar, Rajiv

doi:10.1007/s12018-012-9126-x

Cited by 5 publications

(3 citation statements)

References 50 publications

(54 reference statements)

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“…[22] Vitamin K2-7 plays a role in carboxylating osteocalcin, a Vitamin K-dependent protein, which has been shown to regulate the glucose homeostasis. [23] A decade-long study of 38,094 Dutch population aged 20-70 found that the participants who consumed the most dietary Vitamin K were 20% less likely to develop type 2 diabetes than the participants with the lowest intake of Vitamin K. [22] Vitamin K2 is linked to lowered risk of developing type 2 diabetes. The risk of developing type 2 diabetes drops for every 10 mcg increase in Vitamin K2 intake.…”

Section: Discussionmentioning

confidence: 99%

A Novel Potential Role of Vitamin K2-7 in Relieving Peripheral Neuropathy

Mehta¹,

Dound²,

Jadhav³

et al. 2018

Journal of Pharmacology and Pharmacotherapeutics

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Section: Discussionmentioning

confidence: 99%

A Novel Potential Role of Vitamin K2-7 in Relieving Peripheral Neuropathy

Mehta¹,

Dound²,

Jadhav³

et al. 2018

Journal of Pharmacology and Pharmacotherapeutics

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“…In NAFLD children, there is a positive correlation between ucOCN and ADPN [ 94 ]. In mice, ucOCN enhances ADPN release and improves glucose tolerance [ 95 ].…”

Section: Molecular Mechanism Of Osteocalcin In Flhs Chickensmentioning

confidence: 99%

Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry

Zhang

Jiang

et al. 2023

Animals

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Osteocalcin (OCN) is synthesized and secreted by differentiating osteoblasts. In addition to its role in bone, OCN acts as a hormone in the pancreas, liver, muscle, fat, and other organs to regulate multiple pathophysiological processes including glucose homeostasis and adipic acid metabolism. Fat metabolic disorder, such as excessive fat buildup, is related to non-alcoholic fatty liver disease (NAFLD) in humans. Similarly, fatty liver hemorrhage syndrome (FLHS) is a metabolic disease in laying hens, resulting from lipid accumulation in hepatocytes. FLHS affects hen health with significant impact on poultry egg production. Many studies have proposed that OCN has protective function in mammalian NAFLD, but its function in chicken FLHS and related mechanism have not been completely clarified. Recently, we have revealed that OCN prevents laying hens from FLHS through regulating the JNK pathway, and some pathways related to the disease progression have been identified through both in vivo and vitro investigations. In this view, we discussed the current findings for predicting the strategy for using OCN to prevent or reduce FLHS impact on poultry production.

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“…Dr. Karsenty claimed that we cannot conclude that osteocalcin is not a hormone without the osteocalcin injection experiments. Treatment with vitamin K, which reduces uncarboxylated osteocalcin, does not affect glucose metabolism in humans, and warfarin, which increases uncarboxylated osteocalcin, has no effect on glucose metabolism in rats and there are no reported studies in humans [7,8]. Absence of osteocalcin has no effects on glucose metabolism, testosterone synthesis, and muscle mass in mice [2,3].…”

Section: A1111111111 A1111111111 A1111111111 A1111111111 A1111111111mentioning

confidence: 99%

Lack of reproducibility in osteocalcin-deficient mice

Moriishi

Komori

2020

PLoS Genet

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Reproducibility of data and an author's responsibility to them are extremely important for science. Therefore, researchers repeat experiments and evaluate data objectively and confirm them with various methods. In the comments by Dr. Karsenty, he did not mention the bone phenotypes of osteocalcin-deficient (Ocn-/-) mice, published in Nature in 1996 [1]. That was the first paper describing Ocn-/mice. Ocn-/mice showed a drastic increase in both trabecular and cortical bone due to increased bone formation. Cortical thickness reached to 150% of wild-type mice. However, the bone volumes of both trabecular and cortical bone and bone formation in our Ocn-/mice and Williams's Ocn-/mice were normal [2,3]. Furthermore, the bone phenotypes reported in Karsenty's Ocn-/mice were not reproduced in a recent paper that analyzed bone morphology and showed cortical thickness in the radius was normal [4]. There was another example of a lack of reproducibility in the transgenic mice generated by Karsenty's group and our group. Transgenic mice expressing dominant-negative Runx2 (DNA binding domain only) by Karsenty's group showed drastic reduction in both trabecular and cortical bone, bone formation was reduced to 30% of wild-type mice; the expression of osteocalcin, bone sialoprotein, and osteopontin was virtually abolished; and Col1a1 expression was markedly reduced [5]. These phenotypes were unexpected, because the expression level of dominant-negative Runx2 was much less than endogenous Runx2. The dominant-negative Runx2 inhibits Runx2 in a dose-dependent manner [6]. In our dominant-negative Runx2 transgenic mice, the level of transgene expression was more than ten times higher than endogenous Runx2, but the phenotypes were completely different from those in Karsenty's group. We observed a mild increase in trabecular bone due to reduced bone resorption in our transgenic mice [6]. Since we were unable to reproduce the bone phenotypes of Ocn-/mice, we examined bone quality, glucose metabolism, testosterone synthesis in testis, and muscle mass. Finally, we found a function for osteocalcin in bone. Osteocalcin directs the alignment of apatite crystallites parallel to collagen fibrils. However, we could not find any differences in glucose metabolism, testosterone synthesis in testis, or muscle mass between wild-type and Ocn-/mice. To examine glucose metabolism, we measured body weights, blood glucose levels, HbA1c, and subcutaneous and visceral fat mass, and performed glucose tolerance test (GTT) and insulin tolerance test (ITT) in male and female mice at 11 weeks-18 months of age with normal or high-fat diet. However, all of the glucose metabolism phenotypes were normal in Ocn-/mice. We performed GTT in 58 wild-type and 62 Ocn-/mice, and ITT in 27 wild-type and 24 Ocn-/ mice with normal or high-fat diets. Even if Ocn-/mice were fed a high-fat diet for three months, glucose metabolism was normal [2].

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Osteocalcin and the Regulation of Glucose Metabolism

Cited by 5 publications

References 50 publications

A Novel Potential Role of Vitamin K2-7 in Relieving Peripheral Neuropathy

A Novel Potential Role of Vitamin K2-7 in Relieving Peripheral Neuropathy

Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry

Lack of reproducibility in osteocalcin-deficient mice

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