Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice

Ferron, Mathieu; McKee, Marc D.; Levine, Robert L.; Ducy, Patricia; Karsenty, G.

doi:10.1016/j.bone.2011.04.017

Cited by 365 publications

(317 citation statements)

References 30 publications

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“…This was first established with continuous infusion of osteocalcin through pumps (37) and confirmed with daily i.p. injections (38). In the daily injection protocol for instance, on normal chow, treatment by osteocalcin improved glucose tolerance and insulin sensitivity as well as increased insulin secretion which was accompanied by a significant expansion of the b-cell mass.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

See 1 more Smart Citation

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Confavreux¹,

Szulc²,

Casey³

et al. 2014

European Journal of Endocrinology

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Background: Bone has emerged as an endocrine organ regulating energy metabolism through secretion of osteocalcin. In epidemiological studies, presence of metabolic syndrome (MetS) was associated with lower osteocalcin level. Objectives: We evaluated whether osteocalcin level was associated with MetS severity in men and whether it was more strongly associated with MetS compared with N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (bCTX). Methods: We included 798 men aged 51-85 years for total osteocalcin measurement. Number of MetS criteria was used to define severity. We used polytomous logistic regression to assess the relationship between MetS severity and osteocalcin level. Results: Thirty percent of men had MetS. In patients with MetS, the higher the number of MetS traits were present, the lower was the average osteocalcin level (0-2 criteria: 551 men: 19.5G6.7 ng/ml, three criteria: 155 men: 19.3G7.4 ng/ml, four criteria: 72 men: 17.3G5.7 ng/ml, and five criteria: 20 men: 15.0G5.1 ng/ml; P for trendZ0.002). In the polytomous logistic regression model, an increase in osteocalcin level of 10 ng/ml was associated with lower prevalence of severe MetS: three criteria (odds ratio (OR)Z0.93 (0.70-1.24)), four criteria (ORZ0.54 (0.34-0.84)), and five criteria (ORZ0.28 (0.10-0.82)) in comparison with no MetS (P for trendZ0.008). After adjustment, using stepwise analysis of the polytomous logistic regression model, we observed that osteocalcin, age, and apparent free testosterone entered in the model but not other bone markers (PINP, bCTX, and BAP). Conclusion: In older Caucasian men, total osteocalcin level was associated with MetS severity. Osteocalcin was more strongly associated with MetS severity than other bone turnover markers.

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Section: European Journal Of Endocrinologymentioning

confidence: 99%

“…An increase in energy expenditure through high mitochondrial capacity was also observed. In addition, liver histological analysis after treatment revealed a disappearance of the steatosis (38). Human interventions to increase osteocalcin serum levels have been tested indirectly.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Confavreux¹,

Szulc²,

Casey³

et al. 2014

European Journal of Endocrinology

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“…Sclerostin is secreted by mature osteocytes, inhibiting the Wnt signalling pathway that leads to decreased bone formation and increased muscle differentiation 66. Osteocalcin is a hormone produced by osteoblasts that reduces sensitivity to insulin and enhances the exercise capacity 67, 68. FGF23 induces hypertrophy at least on cardiac muscle, although its effects on skeletal muscle are not fully understood 69.…”

Section: Vitamin D Physiologymentioning

confidence: 99%

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molina

Carrero

Bover

et al. 2017

J cachexia sarcopenia muscle

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The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions.

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“…Treating mice fed a normal diet with recombinant ucOC reduced serum glucose levels and enhanced insulin secretion (27,75). In mice fed a high-fat diet, glucose tolerance and insulin resistance were in part reconstituted and hepatic steatosis regressed by the injection of ucOC (75).…”

Section: Oc As a Treatment: Preclinical Treatment Experimentsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Schwetz

Pieber²,

Obermayer-Pietsch

2012

European Journal of Endocrinology

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Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, b-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated. European Journal of Endocrinology 166 959-967

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Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice

Cited by 365 publications

References 30 publications

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

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