Postnatal loss of the insulin receptor in osteoprogenitor cells does not impart a metabolic phenotype

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2 Scopus citations

Abstract

The relationship between osteoblast-specific insulin signaling, osteocalcin activation and gluco-metabolic homeostasis has proven to be complex and potentially inconsistent across animal-model systems and in humans. Moreover, the impact of postnatally acquired, osteoblast-specific insulin deficiency on the pancreas-to-skeleton-to-pancreas circuit has not been studied. To explore this relationship, we created a model of postnatal elimination of insulin signaling in osteoprogenitors. Osteoprogenitor-selective ablation of the insulin receptor was induced after ~10 weeks of age in IRl°x/lox/Osx-Cre+/− genotypic male and female mice (designated postnatal-OIRKO). At ~21 weeks of age, mice were then phenotypically and metabolically characterized. Postnatal-OIRKO mice demonstrated a significant reduction in circulating concentrations of undercarboxylated osteocalcin (ucOC), in both males and females compared with control littermates. However, no differences were observed between postnatal-OIRKO and control mice in: body composition (lean or fat mass); fasting serum insulin; HbA1c; glucose dynamics during glucose tolerance testing; or in pancreatic islet area or islet morphology, demonstrating that while ucOC is impacted by insulin signaling in osteoprogenitors, there appears to be little to no relationship between osteocalcin, or its derivative (ucOC), and glucose homeostasis in this model.

Original languageEnglish
Article number8842
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
The authors acknowledge and appreciate support for this work, provided by grants from the National Institutes of Health, R56DK084045 (to J.L.F.) and R21AR070620 (to K.M.T); as well as funding from the University of Kentucky Barnstable Brown Diabetes Center Research Endowment. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the listed funding agencies.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • General

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