| RRC ID |
58589
|
| 著者 |
Mizokami A, Mukai S, Gao J, Kawakubo-Yasukochi T, Otani T, Takeuchi H, Jimi E, Hirata M.
|
| タイトル |
GLP-1 signaling is required for improvement of glucose tolerance by osteocalcin.
|
| ジャーナル |
J Endocrinol
|
| Abstract |
Osteocalcin is a bone-derived hormone that in its uncarboxylated form (GluOC) plays an important role in glucose and energy metabolism by stimulating insulin secretion and pancreatic β-cell proliferation through its putative receptor GPRC6A. We previously showed that the effect of GluOC on insulin secretion is mediated predominantly by glucagon-like peptide-1 (GLP-1) released from intestinal endocrine cells in response to GluOC stimulation. Moreover, oral administration of GluOC was found to reduce the fasting blood glucose level, to improve glucose tolerance, and to increase the fasting serum insulin concentration and β-cell area in the pancreas in wild-type mice. We have now examined the effects of oral GluOC administration for at least 4 weeks in GLP-1 receptor-knockout mice. Such administration of GluOC in the mutant mice triggered glucose intolerance, enhanced gluconeogenesis and promoted both lipid accumulation in the liver as well as adipocyte hypertrophy and inflammation in adipose tissue. Furthermore, inactivation of GLP-1 receptor signaling in association with GluOC administration induced activation of the transcription factor FoxO1 and expression of its transcriptional coactivator PGC1α in the liver, likely accounting for the observed upregulation of gluconeogenic gene expression. Our results thus indicate that the beneficial metabolic effects of GluOC are dependent on GLP-1 receptor signaling.
|
| 巻・号 |
244(2)
|
| ページ |
285-296
|
| 公開日 |
2020-2-1
|
| DOI |
10.1530/JOE-19-0288
|
| PII |
JOE-19-0288.R1
|
| PMID |
31693486
|
| MeSH |
Animals
Blood Glucose / metabolism
Female
Forkhead Box Protein O1 / genetics
Forkhead Box Protein O1 / metabolism
Glucagon-Like Peptide 1 / genetics
Glucagon-Like Peptide 1 / metabolism*
Glucose Intolerance / genetics
Glucose Intolerance / metabolism*
Glucose Tolerance Test
Humans
Insulin / metabolism
Insulin-Secreting Cells / metabolism
Kidney / metabolism
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteocalcin / metabolism*
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
Receptors, Glucagon / genetics
Receptors, Glucagon / metabolism
|
| IF |
4.381
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
Hepa 1-6(RCB1638) |
