An Old Friend in a New Light: The Role of Osteocalcin in Energy Metabolism

Sullivan, Tim R.; Duque, Gustavo; Keech, Anthony; Herrmann, Markus

doi:10.1111/j.1755-5922.2011.00300.x

Cited by 13 publications

(41 citation statements)

References 136 publications

(185 reference statements)

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“…Certainly, confirmation through changes in multiple bone formation markers would be consistent with the known effects of insulin on the osteoblast. 12 In fact, in mice, insulin signalling stimulates the synthesis not only of osteocalcin but also of other major matrix proteins, as well as MGP, in osteoblasts. 8 …”

Section: Osteocalcin and Glucose Metabolismmentioning

confidence: 99%

“…The most surprising finding was that only the uncarboxylated or undercarboxylated forms of osteocalcin were active. 5-12 Since those reports, a growing number of studies have linked serum osteocalcin concentrations to glucose homeostasis in humans. This research has led to speculation that serum osteocalcin concentrations have clinical utility as a risk marker for diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

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The role of osteocalcin in human glucose metabolism: marker or mediator?

et al. 2012

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Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent γ-carboxylated form. In circulation, the concentration of osteocalcin is a measure of bone formation. The undercarboxylated form of osteocalcin is reported to be active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans.

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Section: Osteocalcin and Glucose Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of osteocalcin in human glucose metabolism: marker or mediator?

et al. 2012

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“…Serum osteocalcin was negatively correlated with fasting insulin and ‘homeostasis model assessment of insulin resistance’ [34]. Several other reports link high osteocalcin levels to insulin sensitivity [31], but studies in humans have not yet shown direct causal effects [35]. Nevertheless, these studies indicate that osteocalcin supports insulin function and thus storage of energy-rich fuels in adipose tissue and muscle.…”

Section: Energy Storage Hormonesmentioning

confidence: 99%

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

Straub

2014

Arthritis Res Ther

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During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.

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“…The effect of insulin on bone mineral content and on bone strength is difficult to determine as the insulin resistance status of the patient plays a large role in whether insulin has an effect or not. 41 It has proven quite difficult to separate the direct and indirect effects of insulin on bone.…”

Section: Discussionmentioning

confidence: 99%

Impact of Stress-Induced Diabetes on Outcomes in Severely Burned Children

Finnerty

Ali

McLean

et al. 2014

Journal of the American College of Surgeons

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Background Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60-110mg/dL. Because of frequent hypoglycemic episodes, a less stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80-160mg/dL following elevations above 180mg/dL. Study Design We randomized pediatric patients with massive burns into two groups – patients receiving sliding scale insulin to lower blood glucose levels (n=145) and those receiving no insulin (n = 98) to determine the differences in morbidity and mortality. Patients 0-18 years old with burns covering ≥30% of the total body surface area and not randomized to receive anabolic agents were included in this study. Endpoints included glucose levels, infections, resting energy expenditure (REE), lean body mass, bone mineral content (BMC), fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. Results Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent with older children requiring more insulin, p<0.05. Daily maximum and daily minimum, but not 6am,glucose levels were significantly different based on treatment group, p<0.05. Insulin significantly increased REE and improved BMC, p<0.05. Each additional wound infection increased incidence of hyperglycemia, p=0.004. There was no mortality in patients not receiving insulin, only in patients who received insulin (p<0.004). Muscle strength was increased in patients receiving insulin (p<0.05). Conclusions A subset of severely burned children develops burn-induced hyperglycemia. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted BMC and muscle strength, but increased REE, hypoglycemic episodes, and mortality. New glucose-lowering strategies may be needed.

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An Old Friend in a New Light: The Role of Osteocalcin in Energy Metabolism

Cited by 13 publications

References 136 publications

The role of osteocalcin in human glucose metabolism: marker or mediator?

The role of osteocalcin in human glucose metabolism: marker or mediator?

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

Impact of Stress-Induced Diabetes on Outcomes in Severely Burned Children

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