Osteocalcin effect on human β-cells mass and function

Omaima M. Sabek, Satoru Ken Nishimoto, Daniel Fraga, Neelam Tejpal, Camillo Ricordi, A. O. Gaber

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Abstract

The osteoblast-specific hormone osteocalcin (OC) was found to regulate glucose metabolism, fat mass, and β-cell proliferation in mice. Here, we investigate the effect of decarboxylated OC (D-OC) on human β-cell function and mass in culture and in vivo using a Nonobese diabetic-severe combined immunodeficiency mouse model. We found that D-OC at dose ranges from 1.0 to 15 ng/mL significantly augmented insulin content and enhanced human β-cell proliferation of cultured human islets. This was paralleled by increased expression of sulfonylurea receptor protein; a marker of β-cell differentiation and a component of the insulin-secretory apparatus. Moreover, in a Nonobese diabetic-severe combined immunodeficiency mouse model, systemic administration of D-OC at 4.5-ng/h significantly augmented production of human insulin and C-peptide from the grafted human islets. Finally, histological staining of the human islet grafts showed that the improvement in the β-cell function was attributable to an increase in β-cell mass as a result of β-cell proliferation indicated by MKI67 staining together with the increased β-cell number and decreased α-cell number data obtained using laser scanning cytometry. Our data for the first time show D-OC-enhanced β-cell function in human islets and support future exploitation of D-OC-mediated β-cell regulation for developing useful clinical treatments for patients with diabetes.

Original languageEnglish (US)
Pages (from-to)3137-3146
Number of pages10
JournalEndocrinology
Volume156
Issue number9
DOIs
StatePublished - Sep 1 2015

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Sabek, O. M., Nishimoto, S. K., Fraga, D., Tejpal, N., Ricordi, C., & Gaber, A. O. (2015). Osteocalcin effect on human β-cells mass and function. Endocrinology, 156(9), 3137-3146. https://doi.org/10.1210/EN.2015-1143