Details

Autor(en) / Beteiligte

• Tangseefa, Pawanrat
• Martin, Sally K.
• Fitter, Stephen
• Baldock, Paul A.
• Proud, Christopher G.
• Zannettino, Andrew C. W.

Titel

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

Ist Teil von

• Journal of cellular physiology, 2018-05, Vol.233 (5), p.3769-3783

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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 skeletal functions remains in its infancy, the bone‐specific protein, osteocalcin, has been shown to be centrally involved in both processes. This review examines recent data emerging from transgenic mouse models and human clinical studies which have revealed a novel pancreas‐bone‐testis regulatory axis, and discusses the potential role of bone specific mTORC1 signaling in the regulation of systemic glucose metabolism.