4.6 Article

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

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00334.2015

关键词

adiponectin; insulin resistance; osteocalcin; sex difference; testoster-one

资金

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan [24229009, 26861553]
  2. Uehara Memorial Science Foundation
  3. Takeda Science Foundation
  4. Shimabara Science Foundation
  5. Grants-in-Aid for Scientific Research [16K11496, 26861553, 26861554] Funding Source: KAKEN

向作者/读者索取更多资源

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic beta-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 beta-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.

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