The Relationship of Serum Osteocalcin Concentration to Insulin Secretion, Sensitivity, and Disposal with Hypocaloric Diet and Resistance Training

Fernández-Real, José Manuel; Izquierdo, Mikel; Ortega, Francisco; Gorostiaga, Esteban M.; Gómez-Ambrosi, Javier; Moreno-Navarrete, José María; Frühbeck, Gema; Martínez, Cristina; Idoate, Fernando; Salvador, Javier; Forga, Lluís; Ricart, Wifredo; Ibáñez, Javier

doi:10.1210/jc.2008-0270

Cited by 253 publications

(240 citation statements)

References 25 publications

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“…The reduction of visceral fat was the best independent predictor of change in osteocalcin levels, which was positively correlated with insulin sensitivity. Taken together, these results would suggest that physical activity improves insulin sensitivity by increasing serum osteocalcin levels (32).…”

Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 70%

Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Keywords Osteocalcin; undercarboxylated osteocalcin; metabolic syndrome; glucose; energy metabolism; diabetes; obesity; leptin; insulin; adiponectin RESUMO A osteocalcina é uma proteína da matriz óssea que tem sido implicada com várias ações hormonais relacionadas à homeostase de glicose e ao metabolismo energéti-co. Modelos animais e experimentais têm demonstrado que a osteocalcina é liberada do osso para a circulação sanguínea e age nas células betapancreáticas e no tecido adiposo. A osteocalcina decarboxilada é a isoforma hormonalmente ativa e estimula a secreção e sensibilidade à insulina no tecido adiposo e muscular. A insulina e a leptina, por sua vez, atuam no tecido ósseo modulando a secreção da osteocalcina, formando uma alça de retroalimentação tradicional em que o esqueleto torna-se um órgão endócrino. Novos estudos ainda são necessários para elucidar o papel da osteocalcina na regulação glicêmica e no metabolismo energético em humanos, com potenciais implicações terapêuticas no tratamento de diabetes, obesidade e síndrome metabólica. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Descritores

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Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 70%

Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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“…(13) In another study conducted in older healthy men, serum osteocalcin concentrations were inversely associated with blood markers of dysmetabolic phenotype and measures of adiposity. (14) Such studies and others like them (15)(16)(17)(18)(19) suggest that that our proposed endocrine loop comprising insulin, the osteoblast, and osteocalcin represents a conserved regulatory pathway that participates in the global control of glucose metabolism in all bony vertebrates, including humans.…”

Section: From Mice To Humansmentioning

confidence: 73%

The osteoblast: An insulin target cell controlling glucose homeostasis

Clemens

Karsenty

2010

Journal of Bone and Mineral Research

239

174

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The past five years have witnessed the emergence and discovery of unexpected functions played by the skeleton in whole-organism physiology. Among these newly described tasks is the role of bone in the control of energy metabolism, which is achieved through the secretion of osteocalcin, an osteoblasts-derived hormone regulating insulin secretion, insulin sensitivity, and energy expenditure. These initial findings raised several fundamental questions on the nature of insulin action in bone. Discoveries made independently by our two groups have provided answers recently to some of these questions. Through the analysis of mice lacking insulin receptor (InsR) only in osteoblasts, we found that insulin signaling in these cells favors whole-body glucose homeostasis. Importantly, this function of insulin signaling in osteoblasts was achieved through the negative regulation of osteocalcin carboxylation and bioavailability. Our studies also established that insulin signaling in osteoblasts was a positive regulator not only of postnatal bone acquisition but also of bone resorption. Interestingly, it appears that insulin signaling in osteoblasts induced osteocalcin activation by stimulating osteoclast activity. Indeed, the low pH generated during bone resorption is a sufficient means to decarboxylate osteocalcin. Our findings establish that the osteoblast is an important target used by insulin to control whole-body glucose homeostasis and identify bone resorption as the mechanism regulating osteocalcin activation. ß

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“…Thus, osteocalcin was inversely associated with plasma glucose, insulin levels, and serum triglycerides in elderly men and women as well as elderly men with high cardiovascular risk (183,184,185,186,187,188). Also, osteocalcin was lower in patients with T2DM (189,190,191) and gestational diabetes (192).…”

Section: Metabolic Aspects In Relation To a Homeostatic Model Involvimentioning

confidence: 95%

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

Bollerslev

Henriksen

Nielsen

et al. 2013

European Journal of Endocrinology

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Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.

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The Relationship of Serum Osteocalcin Concentration to Insulin Secretion, Sensitivity, and Disposal with Hypocaloric Diet and Resistance Training

Abstract: Circulating osteocalcin could mediate the role of bone as an endocrine organ in humans.

Cited by 253 publications

References 25 publications

Osteocalcin, energy and glucose metabolism

Osteocalcin, energy and glucose metabolism

The osteoblast: An insulin target cell controlling glucose homeostasis

Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies

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