TITLE

Osteocalcin Induces Release of Glucagon-Like Peptide-1 and Thereby Stimulates Insulin Secretion in Mice

AUTHOR(S)
Mizokami, Akiko; Yasutake, Yu; Gao, Jing; Matsuda, Miho; Takahashi, Ichiro; Takeuchi, Hiroshi; Hirata, Masato
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The uncarboxylated form (ucOC), but not the γ-carboxylated form (GlaOC), of the bone-derived protein osteocalcin stimulates insulin secretion and regulates energy metabolism in insulin target tissues. Glucagon-like peptide–1 (GLP-1) is an insulin secretagogue that is released from the gut in response to food intake. We have now found that Gprc6a, a putative ucOC receptor, is expressed in epithelial cells of the mouse small intestine as well as in STC-1 enteroendocrine cells. Secretion of GLP-1 by STC-1 cells was stimulated by ucOC but not by GlaOC. The serum GLP-1 concentration in mice was increased by intraperitoneal or oral administration of ucOC, whereas GlaOC was effective in this regard only after oral application. Serum insulin levels were also increased by ucOC, and this effect was potentiated by an inhibitor of dipeptidyl peptidase IV and blocked by a GLP-1 receptor antagonist. Intravenous injection of ucOC in mice increased the serum GLP-1 concentration, and also increased the serum level of insulin. Our results suggest that ucOC acts via Gprc6a to induce GLP-1 release from the gut, and that the stimulatory effect of ucOC on insulin secretion is largely mediated by GLP-1.
ACCESSION #
87625410

 

Related Articles

  • Long-term, antidiabetogenic effects of GLP-1 gene therapy using a double-stranded, adeno-associated viral vector. Choi, S H; Lee, H C // Gene Therapy;Feb2011, Vol. 18 Issue 2, p155 

    Diabetes is characterized by insulin resistance and a reduction in insulin secretion, leading to progressive β-cell failure and loss of β-cell mass. Its central therapeutic issues are how to restore glucose responsiveness of β-cells to normal and counteract defects in insulin secretion....

  • Reversal of Obesity and Insulin Resistance by a Non-Peptidic Glucagon-Like Peptide-1 Receptor Agonist in Diet-Induced Obese Mice. Min He; Haoran Su; Weiwei Gao; Johansson, Stina M.; Qing Liu; Xiaoyan Wu; Jiayu Liao; Young, Andrew A.; Tamas Bartfai; Ming-Wei Wang // PLoS ONE;2010, Vol. 5 Issue 12, p1 

    Background: Glucagon-like peptide-1 (GLP-1) is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a...

  • Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants. Rueda, Patricia; Harley, Elizabeth; Lu, Yao; Stewart, Gregory D.; Fabb, Stewart; Diepenhorst, Natalie; Cremers, Béatrice; Rouillon, Marie-Hélène; Wehrle, Isabelle; Geant, Anne; Lamarche, Gwladys; Leach, Katie; Charman, William N.; Christopoulos, Arthur; Summers, Roger J.; Sexton, Patrick M.; Langmead, Christopher J. // PLoS ONE;1/19/2016, Vol. 11 Issue 1, p1 

    Phenotyping of Gprc6a KO mice has shown that this promiscuous class C G protein coupled receptor is variously involved in regulation of metabolism, inflammation and endocrine function. Such effects are described as mediated by extracellular calcium, L-amino acids, the bone-derived peptide...

  • The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Flint, A; Raben, A; Rehfeld, J F; Holst, J J; Astrup, A // International Journal of Obesity & Related Metabolic Disorders;Mar2000, Vol. 24 Issue 3, p288 

    OBJECTIVE: To investigate the effects of a near-physiological peripheral glucagon-like peptide-1 (GLP-1) infusion, during and after a breakfast of fixed energy content, on resting energy expenditure, substrate oxidation and metabolism and the desire to eat specific types of food in humans....

  • Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. During, Matthew J.; Cao, Lei; Zuzga, David S.; Francis, Jeremy S.; Fitzsimons, Helen L.; Jiao, Xiangyang; Bland, Ross J.; Klugmann, Matthias; Banks, William A.; Drucker, Daniel J.; Haile, Colin N. // Nature Medicine;Sep2003, Vol. 9 Issue 9, p1173 

    Emphasizes on the expression of the gut peptide glucagon-like (GLP-1) peptide-1 and its receptor GLP-1R in the brain. Enhancement of associative and spatial learning through GLP-1R; Characterization of a phenotype in GLP-1R-deficient mice by a learning deficit; Prevention of kainate-induced...

  • Glucagon-Like Peptide-1 Gene Therapy in Obese Diabetic Mice Results in Long-Term Cure of Diabetes by Improving Insulin Sensitivity and Reducing Hepatic Gluconeogenesis. Lee, Young-Sun; Shin, Seungjin; Shigihara, Toshikatsu; Hahm, Eunsil; Liu, Meng-Ju; Han, Jaeseok; Yoon, Ji-Won; Jun, Hee-Sook // Diabetes;Jun2007, Vol. 56 Issue 6, p1671 

    Long-term treatment with glucagon-like peptide (GLP)-1 or its analog can improve insulin sensitivity. However, continuous administration is required due to its short half-life. We hypothesized that continuous production of therapeutic levels of GLP-1 in vivo by a gene therapy strategy may remit...

  • Generation of Nicotinic Acid Adenine Dinucleotide Phosphate and Cyclic ADP-Ribose by Glucagon-Like Peptide-1 Evokes Ca2+ Signal That Is Essential for Insulin Secretion in Mouse Pancreatic Islets. Byung-Ju Kim; Kwang-Hyun Park; Chang-Yeol Yim; Shin Takasawa; Okamoto, Hiroshi; Mie-Jae Im; Uh-Hyun Kim // Diabetes;Apr2008, Vol. 57 Issue 4, p868 

    OBJECTIVE--Glucagon-like peptide-1 (GLP-1) increases intracellular Ca2+ concentrations ([Ca2+]i), resulting in insulin secretion from pancreatic B-cells. The molecular mechanism(s) of the GLP-1-mediated regulation of [Ca2+]i was investigated. RESEARCH DESIGN AND METHODS--GLP-I-induced changes in...

  • Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity. Cabou, Cendrine; Campistron, Gérard; Marsollier, Nicolas; Leloup, Corinne; Cruciani-Guglielmacci, Celine; Pénicaud, Luc; Drucker, Daniel J.; Magnan, Christophe; Burcelin, Rémy // Diabetes;Oct2008, Vol. 57 Issue 10, p2577 

    OBJECTIVE--To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular...

  • Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing. Knauf, Claude; Cani, Patrice D.; Kim, Dong-Hoon; Iglesias, Miguel A.; Chabo, Chantal; Waget, Aurélie; Colom, André; Rastrelli, Sophie; Delzenne, Nathalie M.; Drucker, Daniel J.; Seeley, Randy J.; Burcelin, Remy // Diabetes;Oct2008, Vol. 57 Issue 10, p2603 

    OBJECTIVE--Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics