Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet

Yu Yasutake, Akiko Mizokami, Tomoyo Kawakubo-Yasukochi, Sakura Chishaki, Ichiro Takahashi, Hiroshi Takeuchi, Masato Hirata

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic β-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic β-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high-fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations.

Original languageEnglish
Pages (from-to)E662-E675
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume310
Issue number8
DOIs
Publication statusPublished - Apr 15 2016

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Osteocalcin
High Fat Diet
Oral Administration
Sucrose
Insulin Resistance
Adiponectin
Adipocytes
Sex Characteristics
Testosterone
Fasting
Insulin
Glucose
Glucose Intolerance
Orchiectomy
Hypertrophy
Energy Metabolism
Blood Glucose
Homeostasis
Cell Proliferation
Hormones

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet. / Yasutake, Yu; Mizokami, Akiko; Kawakubo-Yasukochi, Tomoyo; Chishaki, Sakura; Takahashi, Ichiro; Takeuchi, Hiroshi; Hirata, Masato.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 310, No. 8, 15.04.2016, p. E662-E675.

Research output: Contribution to journalArticle

Yasutake, Yu ; Mizokami, Akiko ; Kawakubo-Yasukochi, Tomoyo ; Chishaki, Sakura ; Takahashi, Ichiro ; Takeuchi, Hiroshi ; Hirata, Masato. / Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 310, No. 8. pp. E662-E675.
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