Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion and pancreatic β-cell proliferation. We previously showed that the effect of GluOC on insulin secretion is mediated largely by glucagon-like peptide-1 (GLP-1) secreted from the intestine in response to GluOC exposure. We have now examined the effect of oral administration of GluOC on glucose utilization as well as the fate of such administered GluOC in mice. Long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level and improved glucose tolerance in mice without affecting insulin sensitivity. It also increased the fasting serum insulin concentration as well as the β-cell area in the pancreas. A small proportion of orally administered GluOC reached the small intestine and remained there for at least 24. h. GluOC also entered the general circulation, and the serum GLP-1 concentration was increased in association with the presence of GluOC in the intestine and systemic circulation. The putative GluOC receptor, GPRC6A was detected in intestinal cells, and was colocalized with GLP-1 in some of these cells. Our results suggest that orally administered GluOC improved glucose handling likely by acting from both the intestinal lumen and the general circulation, with this effect being mediated in part by stimulation of GLP-1 secretion. Oral administration of GluOC warrants further study as a safe and convenient option for the treatment or prevention of metabolic disorders.

Original languageEnglish
Pages (from-to)68-79
Number of pages12
JournalBone
Volume69
DOIs
Publication statusPublished - Sep 16 2014

Fingerprint

Glucagon-Like Peptide 1
Osteocalcin
Oral Administration
Glucose
Insulin
Intestines
Fasting
Serum
Energy Metabolism
Small Intestine
Insulin Resistance
Blood Glucose
Pancreas
Cell Proliferation
Hormones
Bone and Bones
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion. / Mizokami, Akiko; Yasutake, Yu; Higashi, Sen; Kawakubo-Yasukochi, Tomoyo; Chishaki, Sakura; Takahashi, Ichiro; Takeuchi, Hiroshi; Hirata, Masato.

In: Bone, Vol. 69, 16.09.2014, p. 68-79.

Research output: Contribution to journalArticle

Mizokami, Akiko ; Yasutake, Yu ; Higashi, Sen ; Kawakubo-Yasukochi, Tomoyo ; Chishaki, Sakura ; Takahashi, Ichiro ; Takeuchi, Hiroshi ; Hirata, Masato. / Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion. In: Bone. 2014 ; Vol. 69. pp. 68-79.
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