Association between osteocalcin and glucose metabolism: a meta-analysis

Liu, D.-M.; Guo, Xuejun; Tong, Hongxuan; Tao, Bei; Sun, Liya; Zhao, Hui; Ning, Guang; Liu, J.-M.

doi:10.1007/s00198-015-3197-8

Cited by 57 publications

(44 citation statements)

References 65 publications

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“…Elevated levels of total OCN are also associated with lower fasting glucose and acetylated hemoglobin (HbA1c) levels, higher insulin secretion and increased serum adiponectin levels in both diabetic and non‐diabetic patients (Jung et al, ), and lower levels of unOCN are associated with impaired glucose tolerance in children (Pollock et al, ). Interestingly, untreated T2DM and pre‐diabetic patients exhibit decreased levels of unOCN and total OCN, and increased OCN levels are associated with improved β‐cell function (Liu et al, ). A recent Japanese study of T2DM patients also found that levels of unOCN positively correlate with the C‐peptide response in glucagon loading and meal tolerance tests, suggesting that unOCN could be used for the assessment of insulin secretion in patients with T2DM (Takashi et al, ).…”

Section: Endocrine Roles Of Ocn In Humansmentioning

confidence: 99%

Osteocalcin‐dependent regulation of glucose metabolism and fertility: Skeletal implications for the development of insulin resistance

Tangseefa

Martin

Fitter

et al. 2017

Journal Cellular Physiology

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The skeleton has recently emerged as a critical insulin target tissue that regulates whole body glucose metabolism and male reproductive function. While our understanding of these new regulatory axes remains in its infancy, the bone-specific protein, osteocalcin, has been shown to be centrally involved. Undercarboxylated osteocalcin acts as a secretagogue in a feed-forward loop to stimulate pancreatic β-cell proliferation and insulin secretion, improve insulin sensitivity, and promote testosterone production. Importantly, dysregulation of insulin signaling in bone causes a reduction in serum osteocalcin levels that is associated with elevated blood glucose and reduced serum insulin levels, suggesting that the skeleton may play a significant role in the development of diet-induced insulin resistance. Insulin signaling is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) which becomes hyper-activated in response to nutrient overload. Loss- and gain-of function models suggest that mTORC1 function in bone is essential for normal skeletal development; however, the role of this complex in the regulation of glucose metabolism remains to be determined. This review highlights our current understanding of the role played by osteocalcin in the skeletal regulation of glucose metabolism and fertility. In particular, it examines data emerging from transgenic mouse models which have revealed a pancreas-bone-testis regulatory axis and discusses recent human studies which seek to corroborate findings from mouse models with clinical observations. Moreover, we review recent studies which suggest dysregulation of insulin signaling in bone leads to the development of insulin resistance and discuss the potential role of mTORC1 signaling in this process.

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Section: Endocrine Roles Of Ocn In Humansmentioning

confidence: 99%

Osteocalcin‐dependent regulation of glucose metabolism and fertility: Skeletal implications for the development of insulin resistance

Tangseefa

Martin

Fitter

et al. 2017

Journal Cellular Physiology

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“…5 In the last 10 years, mounting evidence from mouse models has suggested a promising role of the skeleton in regulating glucose homeostasis, mainly through a bone protein synthesized by osteoblasts called osteocalcin (OCN), which can stimulate insulin release from β cells and improve insulin sensitivity. 6,7,8,9 Although most, but not all, human cross-sectional investigations lend support to the negative associations between the bone formation marker OCN and fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c), 10 data from a limited number of longitudinal human studies are not consistent. 11,12 …”

Section: Introductionmentioning

confidence: 99%

The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years

Liu

Yang

et al. 2017

Bone Res

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Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin (OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen (CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant (NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% (95% confidence interval (CI), 6.8%–30.7%)] compared with the lower [31.0% (95% CI, 17.2%–46.1%)] and upper [46.5% (95% CI, 31.2%–62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles (P=0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73–28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.

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“…In addition to these observations in mouse studies and in vitro investigations, the relationships between OCN and glucose‐related parameters have been examined in humans. Generally, in cross‐sectional studies, higher serum levels of OCN were negatively related to fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) in T2DM . However, whether such an inverse association is the result of the effect of OCN on glucose or a reflection of altered bone turnover in dysglycaemia is unclear, as diabetes patients usually have lower levels of bone formation .…”

Section: Osteoblast‐derived Ocn As An Insulin Secretagogue and Insulimentioning

confidence: 99%

“…Several large‐scale human studies from Japan and China demonstrated that a lower baseline serum OCN level, for example, less than 6 ng/mL, was associated with increased risk of future development of T2DM and prediabetes . Thus, the predictive value of OCN with respect to incident dysglycaemia and diabetes should be further tested and verified in different ethnic populations …”

Section: Osteoblast‐derived Ocn As An Insulin Secretagogue and Insulimentioning

confidence: 99%

Bone: Another potential target to treat, prevent and predict diabetes

Liu¹,

Mosialou

Liu

2018

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.

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Association between osteocalcin and glucose metabolism: a meta-analysis

Abstract: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women.

Cited by 57 publications

References 65 publications

Osteocalcin‐dependent regulation of glucose metabolism and fertility: Skeletal implications for the development of insulin resistance

Osteocalcin‐dependent regulation of glucose metabolism and fertility: Skeletal implications for the development of insulin resistance

The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years

Bone: Another potential target to treat, prevent and predict diabetes

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