Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a

Wei, Jianwen; Hanna, Timothy P.; Suda, Nina; Karsenty, G.; Ducy, Patricia

doi:10.2337/db13-0887

Cited by 220 publications

(202 citation statements)

References 43 publications

Supporting

Mentioning

189

Contrasting

Unclassified

Order By: Relevance

“…Recent emerging results from two independent laboratories have indicated that, in addition to Glut4, Glut1 is necessary for bone formation and whole-body glucose homoeostasis. Moreover, Glut1 is modulated by high glucose levels (Virta et al 2014, Wei et al 2014a. Collectively, these results provide a deeper understanding of the role of bone in the regulation of glucose metabolism (summarised in Fig.…”

Section: Glucose Transporter and Bonementioning

confidence: 88%

“…injection of OC failed to markedly stimulate ERK activity, thus having minor effects on circulating serum insulin levels, which were increased in WT mice exposed to the same treatment. GPRC6A has been shown to be integral in the promotion of b-cell proliferation during development and adulthood via OC, thus highlighting GPRC6A as an important receptor for skeletal-tissue-mediated energy regulation via the pancreas (Pi et al 2011, Wei et al 2014a. Most recently, Oury et al (2013) demonstrated that OC acts via a pancreas-bone-testis axis, such that OC-stimulated testosterone synthesis is positively regulated by insulin signalling in osteoblasts and is independent of luteinising hormone (LH).…”

Section: Male Fertility and The Discovery Of The Oc Receptormentioning

confidence: 99%

See 1 more Smart Citation

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

102

View full text Add to dashboard Cite

Recent developments in endocrinology, made possible by the combination of mouse genetics, integrative physiology and clinical observations have resulted in rapid and unanticipated advances in the field of skeletal biology. Indeed, the skeleton, classically viewed as a structural scaffold necessary for mobility, and regulator of calcium-phosphorus homoeostasis and maintenance of the haematopoietic niche has now been identified as an important regulator of male fertility and whole-body glucose metabolism, in addition to the classical insulin target tissues. These seminal findings confirm bone to be a true endocrine organ. This review is intended to detail the key events commencing from the elucidation of osteocalcin (OC) in bone metabolism to identification of new and emerging candidates that may regulate energy metabolism independently of OC.Key WordsJournal of Endocrinology (2015) 225, R1-R19

show abstract

Section: Glucose Transporter and Bonementioning

confidence: 88%

Section: Male Fertility and The Discovery Of The Oc Receptormentioning

confidence: 99%

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

102

View full text Add to dashboard Cite

show abstract

“…Według Wei i wsp. [1] może ona mieć wpływ na metabolizm glukozy, uwalnianie insuliny i stymulację insulinowrażliwości. Badania tych autorów wskazują na potencjalny wpływ osteokalcyny na stymulację proliferacji komórek beta trzustki zarówno w okresie okołoporodowym, jak i u dorosłych.…”

Section: Osteokalcyna I Osteoprotegeryna/ Rankl a Trzustkaunclassified

Type 1 diabetes mellitus and dysfunction of bone status

Szewczyk¹,

Bury²

2014

Pediatr. Endocrinol.

View full text Add to dashboard Cite

STRESZCZENIE/ABSTRACTRelacje między metabolizmem tkanki kostnej a mechanizmami regulującymi gospodarkę węglowodanową nie wydają się bezpośrednie, choć nie są dostatecznie poznane, a przecież uważa się że tkanka kostna wykorzystuje znaczną pulę glukozy przyswajanej przez organizm. Prześledzono relacje między markerami kościotworzenia a działaniem insuliny, zachowanie tych markerów w przebiegu cukrzycy typu 1, równoległość procesów angiogenezy i osteogenezy oraz uwarunkowania osteopenii w cukrzycy typu 1. Endokrynol. Ped. 13/2014;4(49):35-40. The relationship between the bone metabolism and the mechanisms regulating carbohydrate homeostasis does not appear to be direct, but are not sufficiently known, and yet it is believed that bone tissue is using the large pool of the glucose acquired by the organism. The relationship between markers of bone formation and action of insulin, the behavior of these markers in type 1 diabetes, the parallel processes of angiogenesis and osteogenesis and conditions of osteopenia in type 1 diabetes have been assessed. Pediatr. Endocrinol. 13/2014;4(49) rozpuszczania i resorpcji tkanki kostnej, co ma znaczenie w prawidłowym kształtowaniu się struktury kości. Osteoblasty wytwarzają zaś część organiczną macierzy kostnej, w której odkładają się związ-ki fosforanów wapnia. Proces ten jest regulowany przez parathormon i wit. D.Relacje między metabolizmem tkanki kostnej a mechanizmami regulującymi gospodarkę węglo-wodanową nie są dostatecznie poznane i nie wydają się bezpośrednie i proste.Jak wiadomo, kości są ciągle przebudowywane, zużytą tkankę kostną zastępuje nowa. Proces ten zachodzi przy pomocy dwu typów komórek: osteoblastów i osteoklastów. Osteoklasty mają zdolność

show abstract

“…In this issue, Wei et al (18) show that pancreatic b-cell mass is controlled during development and adulthood by osteocalcin via its receptor Gprc6a. Recently, several observations have highlighted that bone, more than supporting tissue, is a real endocrine organ regulating various functions including glucose metabolism and energy expenditure.…”

mentioning

confidence: 99%

When the Skeleton Is Controlling Pancreatic β-Cell Mass During Development and After

Bouckenooghe

Lefebvre

2014

Diabetes

View full text Add to dashboard Cite

The understanding of the phenomenon leading to pancreatic b-cell mass regulation represents a critical step in the development of regenerative therapy for diabetic patients. Type 1 (T1D) and type 2 (T2D) diabetes are characterized by a near-absolute or a relative deficiency of b-cells numbers, respectively. In T1D, at the time of clinical diagnosis, approximately 60-80% of the insulinproducing cells have been destroyed (1). With the currently available treatments, patients with T1D and T2D develop severe long-term complications that clearly reduce their life expectancy (2-4). While insulin replacement continues to be the primary treatment, the need to establish a precise and physiological glucoregulation in order to avoid complications has led to multiple avenues of alternative interventions. Some studies fulfilled this requirement with allogenic transplantation of human islets or insulin-producing cells (5,6). Still under extensive study, the use of pig islets as an alternative source of insulin-producing cells for xenotransplantation seems to be promising and could represent the future of cell therapy for diabetes (7). Other studies have aimed at abrogating the cause of the disease (i.e., the autoimmunity leading to the destruction of b-cells in T1D) (8). Finally, others worked on the reestablishment of an adequate b-cell mass able to restore euglycemia through methods that promote b-cell preservation and/or regeneration in diabetic individuals (9-11).Pancreatic b-cell mass and function exhibit significant plasticity so that in times of increased insulin demand, such as obesity (12), insulin resistance, and pregnancy (13,14), b-cell numbers and insulin secretory capacity can increase significantly to meet this metabolic demand.During a life span, maintenance of pancreatic b-cell mass is regulated by a complex equilibrium among neogenesis, increase and decrease of cell volume (hypertrophy or atrophy), cell differentiation, and cell proliferation (hyperplasia) and death (apoptosis). Now, there is considerable interest in finding efficient and safe methods to increase b-cell mass by inducing the proliferation of remaining b-cells or favoring the differentiation of resident precursors or progenitors. The proliferation of preexisting b-cells has been shown to be an important source of newly derived adult pancreatic b-cells (15). Under physiological conditions, the rate of primary b-cell replication is very low (in the range of 0-1.2% of the b-cells in adults). Although extensively studied, physiological mechanisms of human b-cell proliferation still remain unknown. Different molecules have been shown to favor b-cell proliferation, mainly prolactin (increasing during pregnancy), serotonin (16), glucagon-like peptide 1 (GLP-1), and betatrophin (17).In this issue, Wei et al. (18) show that pancreatic b-cell mass is controlled during development and adulthood by osteocalcin via its receptor Gprc6a. Recently, several observations have highlighted that bone, more than supporting tissue, is a real endocrine organ regulat...

show abstract

Osteocalcin Promotes β-Cell Proliferation During Development and Adulthood Through Gprc6a

Cited by 220 publications

References 43 publications

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Type 1 diabetes mellitus and dysfunction of bone status

When the Skeleton Is Controlling Pancreatic β-Cell Mass During Development and After

Contact Info

Product

Resources

About