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

Mizokami, Akinari; Yasutake, Yu; Gao, Jing; Matsuda, Miho; Takahashi, Ichiro; Takeuchi, Hiroshi; Hirata, Masato

doi:10.1371/journal.pone.0057375

Cited by 150 publications

(140 citation statements)

References 30 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…An identical volume of sterilized PBS was injected as a control. A glucose tolerance test was performed according to previous reports (55,56). Briefly, 2 min after injection of DPP4, a glucose solution (3 mg/g of body weight) was orally administered and blood glucose levels were measured at 0, 10, 30, 60, and 120 min using an OneTouch Ultravue device (Johnson & Johnson, New Brunswick, NJ).…”

Section: Discussionmentioning

confidence: 99%

Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4

et al. 2017

View full text Add to dashboard Cite

Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels. Cellassociated DPP4 activity was found in those microorganisms, which was effectively suppressed by inhibitors of human DPP4, and molecules sized 73 kDa in P. gingivalis, and 71 kDa in T. forsythia and P. intermedia were immunologically detected. The k cat /K m values of recombinant DPP4s ranged from 721 Ϯ 55 to 1,283 Ϯ 23 M Ϫ1 s Ϫ1 toward Gly-Pro-4-methylcoumaryl-7-amide (MCA), while those were much lower for His-Ala-MCA. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis showed His/Tyr-Ala dipeptide release from the N termini of incretins, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, respectively, with the action of microbial DPP4. Moreover, intravenous injection of DPP4 into mice decreased plasma active GLP-1 and insulin levels, accompanied by a substantial elevation in blood glucose over the control after oral glucose administration. These results are the first to show that periodontopathic bacterial DPP4 is capable of modulating blood glucose levels the same as mammalian DPP4; thus, the incidence of periodontopathic bacteremia may exacerbate diabetes mellitus via molecular events of bacterial DPP4 activities.

show abstract

Section: Discussionmentioning

confidence: 99%

Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Importantly, uncarboxylated form of OCN promotes insulin secretion to affect glucose metabolism by means of stimulating glucagons-like peptide-1 (GLP-1) [55]. OCN circulation can be attenuated by dietary phosphorus supplementation [56], implying functions of phosphorus in regulating OCN secretion and function.…”

Section: Discussionmentioning

confidence: 99%

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Zou

Xiong

Lai

et al. 2015

Sci. China Life Sci.

View full text Add to dashboard Cite

Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice (PUG), a model of human X-linked hypophosphatemic rickets (XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus-and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin (OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients. glucose metabolism, mineral homeostasis, bone, Phex, X-linked hypophosphatemic rickets Citation:Zou JH, Xiong XW, Lai BB, Sun M, Tu X, Gao X. Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model. [5,6]. In the past decades, bone was studied as an endocrinal organ [7,8]. Interactions between bone and energy metabolism aroused extensive interests and concerns [911]. Phex is mainly expressed in osteoblasts and odontoblasts [1214] and its mutations lead to reduced 1,25-(OH) 2 D 3 and elevated circulating FGF23 (fibroblast growth factor 23) [1517]. 1,25-(OH) 2 D 3 and its receptor could influence expression of uncoupling protein (UCP) in adipocytes [18,19]. In vitro studies demonstrate that the role of 1,25-(OH) 2 D 3 in lipid metabolism is regulator of peroxisome proliferator-activated receptor alpha (Ppara) [20]. Circulating FGF23 is also associated with fat mass and serum lipids [21]. In mouse models of XLH, like Hyp mice, decreased renal glucose reabsorption activity [22], increased glucose production in renal proximal tubules [23] and osteoblasts [24] were observed. The only known physiological substrate of PHEX protein, acidic serine aspartate-rich MEPE associated motif (ASARM peptide), could regulate glucose metabolism and insulin signaling [14]. The above findings indicate PHEXmediated association between skeletal function and energy

show abstract

“…In addition, hepatic steatosis induced by a high-fat diet was completely recovered in mice treated with daily osteocalcin injection. Interestingly, the oral administration of osteocalcin also improved impaired glucose tolerance in vivo 38,39,41) . The ucOC via oral administration reached the small intestines, remained there for at least 24 h, and entered the general circulation.…”

Section: Glucose Metabolism Regulation By Osteocalcinmentioning

confidence: 98%

“…In addition to the direct effect of osteocalcin on insulin secretion, osteocalcin indirectly stimulates insulin expression and secretion by increasing the secretion of glucagon-like peptide-1 (GLP-1), which is an incretin released by intestinal endocrine cells. Mizokami et al demonstrated that the treatment with ucOC significantly increased GLP-1 expression in STC-1 enteroendocrine cells in vitro and that the administration of ucOC increased serum GLP-1 and insulin levels in mice 38,39) . These effects were potentiated by an inhibitor of dipeptidyl peptidase-4 and blocked by a GLP-1 receptor antagonist, suggesting that ucOC increases insulin secretion by enhancing GLP-1 secretion from intestinal endocrine cells.…”

Section: Glucose Metabolism Regulation By Osteocalcinmentioning

confidence: 99%

Association of the roles of advanced glycation end products and osteocalcin between bone metabolism and vascular failure

Kanazawa

2017

Vasc Fail

View full text Add to dashboard Cite

Abstract:Fragility fracture impairs the activities of daily living and quality of life of the elderly. Accumulating evidence has shown that patients with osteoporosis have an increased all-cause mortality as well as cardiovascular mortality rates. Osteoporosis and cardiovascular diseases have common risk factors, such as diabetes mellitus. Patients with diabetes have an increased risk of osteoporosis; thus, diabetes-related bone disease is now recognized as one of the complications of diabetes. Although accumulation of advanced glycation end products and oxidative stress are associated with the formation and progression of atherosclerosis, these are reported to be involved in the pathogenesis of osteoporosis, especially in diabetic patients. Moreover, recent studies have shown that osteocalcin, which is secreted from the bone into the circulation, has an endocrine function of regulating glucose and energy metabolism. In addition, osteocalcin directly affects vascular endothelial cells and smooth muscle cells and protects against oxidative stress-induced cell dysfunction. Therefore, the bone-vascular axis attracts widespread attention. In this review, I described the association between bone and glucose metabolism and vascular failure on the basis of recent evidence.

show abstract

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

Cited by 150 publications

References 30 publications

Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4

Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Association of the roles of advanced glycation end products and osteocalcin between bone metabolism and vascular failure

Contact Info

Product

Resources

About