• Title/Summary/Keyword: TGR5

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Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis

  • Kim, Hyeonhui;Fang, Sungsoon
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.140-146
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    • 2018
  • Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism

  • Tian, Fengyuan;Huang, Shuo;Xu, Wangda;Chen, Lan;Su, Jianming;Ni, Haixiang;Feng, Xiaohong;Chen, Jie;Wang, Xi;Huang, Qi
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.780-789
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    • 2022
  • Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

Comparison of the Effects of Magnetically Controlled Growing Rod and Tradiotinal Growing Rod Techniques on the Sagittal Plane in the Treatment of Early-Onset Scoliosis

  • Erdogan, Sinan;Polat, Baris;Atici, Yunus;Ozyalvac, Osman Nuri;Ozturk, Cagatay
    • Journal of Korean Neurosurgical Society
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    • v.62 no.5
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    • pp.577-585
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    • 2019
  • Objective : Comparing the effects of magnetically controlled growing rod (MCGR) and traditional growing rod (TGR) techniques on the sagittal plane in the treatment of early-onset scoliosis (EOS). Methods : Twelve patients were operated using dual MCGR technique in one center, while 15 patients were operated using dual TGR technique for EOS in another center. Patients' demographic characteristics, complications and radiological measurements such as cobb angle, thoracic kyphosis, lumbar lordosis, T1-S1 range (mm), proximal junctional angle, distal junctional angle, sagittal balance, coronal balance, pelvic incidence, sacral slope and pelvic tilt were assessed and compared in preoperative, postoperative and last follow-up period. Results : Age and sex distributions were similar in both groups. The mean number of lengthening in the MCGR group was 12 (8-15) and 4.8 (3-7) in the TGR group. Two techniques were shown to be effective in controlling the curvature and in the increase of T1-S1 distance. In TGR group, four patients had rod fractures, six patients had screw pull-out and four patients had an infection, whereas three patients had screw pull-out and one patient had infection complications in the MCGR group. Conclusion : There was no significant difference between the two groups in terms of cobb angle, coronal and sagittal balance and sagittal pelvic parameters. MCGR can cause hypokyphosis and proximal junctional kyphosis in a minimum 2-year follow-up period. The implant-related complications were less in the MCGR group. However, larger case groups and longer follow-up periods are required for the better understanding of the superiority of one method on other in terms of complications.

FDG PET/CT Assessment of the Biological Behavior of Meningiomas

  • Park, Yong-Sook;Jeon, Byung-Chan;Oh, Hyung-Suk;Lee, Seok-Mo;Chun, Bong-Kwon;Chang, Hee-Kyung
    • Journal of Korean Neurosurgical Society
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    • v.40 no.6
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    • pp.428-433
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    • 2006
  • Objective : We investigated the pattern of glucose uptake in meningiomas using $^{18}F$-fluoro-2-deoxy-D-glucose[FDG] PET/CT. It was hypothesized that the degree of glucose uptake in each tumor could predict the histologic grade. Methods : In 19 patients with meningiomas, the Ki-67 proliferative index, standardized uptake values[SUV] of FDG uptake, tumor to contralateral gray matter ratio[TGR] of SUV, tumor size, edema grade, vascular endothelial growth factor[VEGF] expression, histopathologic grade and the blood supply pattern were assessed. Results : Of the 19 meningiomas, 8 were meningothelial, 1 fibrous, 2 transitional, 1 psammomatous, 2 angiomatous, and 5 atypical. The tumor proliferative index of Ki-67, tumor size, and peritumoral edema were larger in the histopathologic grade-2 meninigiomas than in the grade-1 meningioma group. There were no significant differences in SUV and TGR between two groups. Tumor size and peritumoral edema were significantly larger in VEGF-positive tumors than in negative tumors. Conventional angiography was performed in 12 patients. Dural supply was noted predominantly in 2 patients. Four patients had mainly pial cortical supply patterns. In tumors with more pial supply, VEGF was more frequently positive. There was a significant relation between SUV and Ki-67 and between SUV and peritumoral edema. Conclusion : We found FOG uptake in meningiomas is associated with proliferative potential, however, no clear limits of SUV and TGR can be set to distinguish between grade-1 and grade-2 meningiomas, which makes the assessment of malignancy grade using PET scan metabolic imaging difficult in individual cases.

The Regulatory Role of Chenodeoxycholic Acid on the Proliferation of Osteoclast Precursor Cells (Chenodeoxycholic Acid에 의한 파골전구세포의 증식 조절)

  • Noh, A Long Sae Mi;Yim, Mijung
    • YAKHAK HOEJI
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    • v.58 no.3
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    • pp.165-170
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    • 2014
  • We investigated the effect of Chenodeoxycholic acid (CDCA) on the proliferation of osteoclast precursor cells. CDCA decreased the proliferation of osteoclast precursor cells through the control of cell cycle regulators such as cyclin D1, p21 and p27. When we checked the signaling pathway, CDCA decreased Erk activation in osteoclast precursor cells. Furthermore, two bile acid receptors, FXR and TGR5, were involved in the suppressive effect of CDCA. Taken together, this study suggested that bile acid plays an important role in the proliferation of osteoclast precursor cells.

Impact of Transplanting on Tree Growth and Compartmentalization of Pruning Wounds in Acer palmatum Thunb

  • Lee, Kyu Hwa;Lee, Kyung Joon;Gwak, Ki-Seob;Choi, In-Gyu
    • Journal of Korean Society of Forest Science
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    • v.98 no.5
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    • pp.618-629
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    • 2009
  • The objective of this study was to examine the impact of pruning (P treatment) and transplanting (T treatment) of Acer palmatum on cambial growth and compartmentalization of pruning wounds for one year after treatments. Changes of cambial electrical resistance (CER), sizes of pruning wounds, cambial growth of trunks and stems near the wounds, and total phenols at branch unions during the period were examined using a total of 49 trees. After harvesting, areas of discolored wood behind the wounds, relative proportions of extractives, holocellulose and lignin at branch unions were also determined. CER and the cambial growth of trunk at 30 cm above the ground (TGR) were inversely correlated, and differences of CER and TGR among three treatments were significant. TGRs of control, P treatment and P+T treatment after the treatments were 112.2%, 72.4% and 52.5% of the annual growth for the year before the treatments, respectively. The cambial growth rate of stem (SGR) at 1.5 cm above the branch bark ridge and the closure rate of pruning wound (WCR) for one year after treatments were positively correlated, and WCR of P treatment of 39.8% was significantly higher than that of P+T treatment of 31.8%. Wounds of P+T treatment formed greater discolored area per unit area of pruning wound (D/W Ratio) than those of P treatment significantly. Lower WCR and higher D/W Ratio of P+T treatment suggested less ability of compartmentalizing the wounds than P treatment. Total phenols at branch core of pruning wound for both treatments heightened a month after treatment, and then lowered. The contents at below core of the wound were higher than those at control ones continuously, while they became similar each other at above core. Relatively high phenol contents of the extractives at P+T treatment implied that trees with P+T treatment allocated more energy to compartmentalize their wounds. Holocellulose and lignin contents at the branch core of treated branch unions of both treatments were lower and higher, respectively, than at the same part of the union with living branch, as results of the tree reaction to protection from wounding and microbial invasion.

A Bisdesmosidic Cholestane Glycoside from the Rhizomes of Polygonatum sibiricum

  • Ahn, Mi-Jeong;Cho, Hee-Yeong;Lee, Mi-Kyeong;Bae, Ji-Yeong;Choi, Jang-Gyoo;Kim, Chul-Young;Kim, Jin-Woong
    • Natural Product Sciences
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    • v.17 no.3
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    • pp.183-188
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    • 2011
  • A bisdesmosidic cholestane glycoside was isolated from the rhizomes of Polygonatum sibiricum and the structure was elucidated by spectroscopic methods and acid hydrolysis as (22S)-cholest-5-ene-$1{\beta}$,$3{\beta}$,$16{\beta}$,22-tetrol 1-O-${\alpha}$-L-rhamnopyranosyl 16-O-${\beta}$-D-glucopyranoside. This compound exhibited weak cytotoxic activity with the $IC_{50}$ value, $63.6\;{\mu}M$ in human MCF-7 breast cancer line, whereas it failed to show agonistic activity at $100{\mu}M$ in TGR5 assay with Chinese hamster ovary (CHO) cells. This is the first report of a bisdesmosidic cholestane glycoside from Polygonatum species and the full assignments of $^1H$, $^{13}C$ NMR by HMBC, TOCSY and NOESY experiments were provided.

Food 3D Printing Technology and Food Materials of 3D Printing (식품 3D 프린팅 기술과 3D 프린팅 식품 소재)

  • Kim, Min-Jeong;Kim, Mi-Kyung;You, Young-Sun
    • Clean Technology
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    • v.26 no.2
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    • pp.109-115
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    • 2020
  • Over the last 3 years, the global food 3D printing market has grown at an average annual rate of 31.5% and has shown an industry size that reached about U$ 9.46 billion. Food 3D printing technology has the advantage of being utilizable in diverse ranges because it enables free design of existing foods so that foods can be produced according to individuals' tastes and purposes. Many countries around the world are producing food 3D printers to release trial products such as foods employing the advantages of food 3D printing. They are also attempting to apply food 3D printing in various fields such as combat rations, space rations, restaurants, liquid foods, foods for the elderly, diets for patients, and baby foods. Whereas the 3D printing market, which has a high growth potential and is expected to continue to expand in size, is highly likely to become a blue ocean, not only is food 3D printing technology small in South Korea, but also the overall ratio of 3D printing utilization and the scale of the relevant industry are small. This is attributable to the fact that South Korea has problems such as insufficient institutionalization compared to developed countries and delays in the development of standardized domestic materials. Therefore, this paper is intended to inform the necessity of food 3D printing and describe food 3D printing technology and food 3D materials in order to obtain the additional effect of vitalizing the South Korean food 3D printing market.

Changes of Polyamine Metabolism and Delayed Neuronal Degeneration of Hippocampus after Transient Cerebral Ischemia in Mongolian Gerbils (뇌허혈 손상에 있어서 Polyamine 대사의 변동이 해마신경세포의 지연성괴사에 미치는 효과에 관한 연구)

  • Shin, Kyung-Ho;Shin, Hwa-Jung;Lee, Young-Jae;Kim, Hyung-Gun;Choi, Sang-Hyun;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.323-334
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    • 1996
  • Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

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