scholarly journals Davidones F and G, Two Novel Flavonoids from Sophora davidii (Franch.) Skeels

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4182
Author(s):  
Ping Song ◽  
Xuecui Li ◽  
Tongxi Zhou ◽  
Yu Peng ◽  
Ho-Young Choi ◽  
...  

An unprecedented novel flavanone davidone F (1) with a seven-membered ring side chain, and a novel flavanonol davidone G (2), along with 11 known flavonoids, were isolated from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. Their planar structures were established by UV, IR, HRESIMS, 1D and 2D NMR data. The relative configurations of 1 and 2 were determined by calculation of NMR chemical shift values, the absolute configuration of 1 and 2 were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Moreover, compounds 1–13 were screened for the translocation activity of glucose transporter 4 (GLUT-4), and the fluorescence intensity was increased to the range of 1.56 and 2.79 folds. Compounds 1 and 2 showed moderate GLUT-4 translocation activity with 1.64 and 1.79 folds enhancement, respectively, at a concentration of 20 μg/mL.

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 756
Author(s):  
Kangdi Li ◽  
Yuanren Ma ◽  
Tongxi Zhou ◽  
Xinzhou Yang ◽  
Ho-Young Choi

Sophora davidii (Franch.) Skeels is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of S. davidii, a chemical investigation was thus performed. In this research, two new stilbene oligomers, Davidiol E–F (1–2), one new 4-aryl-substituted isoflavan Davidinin A (3), and one new 2-arylbenzofuran dimer, Shandougenine C (4), as well as six known compounds (5–10) were obtained from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. The absolute configuration of 1–3 was assigned by comparing its experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1–10 promoted glucose transporter 4 (GLUT-4) translocations by the range of 1.28–2.60 folds, respectively. Compound 9 showed the most potent glucose transporter 4 translocations with 1.60 fold enhancement. The result attained in this study indicated that the separation and characterization of these compounds plays an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.


Endocrinology ◽  
1997 ◽  
Vol 138 (5) ◽  
pp. 2005-2010 ◽  
Author(s):  
Jean-François Tanti ◽  
Sophie Grillo ◽  
Thierry Grémeaux ◽  
Paul J. Coffer ◽  
Emmanuel Van Obberghen ◽  
...  

Abstract Phosphatidylinositol 3-kinase (PI 3-kinase) activation promotes glucose transporter 4 (Glut 4) translocation in adipocytes. In this study, we demonstrate that protein kinase B, a serine/threonine kinase stimulated by PI 3-kinase, is activated by both insulin and okadaic acid in isolated adipocytes, in parallel with their effects on Glut 4 translocation. In 3T3-L1 adipocytes, platelet-derived growth factor activated PI 3-kinase as efficiently as insulin but was only half as potent as insulin in promoting protein kinase B (PKB) activation. To look for a potential role of PKB in Glut 4 translocation, adipocytes were transfected with a constitutively active PKB (Gag-PKB) together with an epitope tagged transporter (Glut 4 myc). Gag-PKB was associated with all membrane fractions, whereas the endogenous PKB was mostly cytosolic. Expression of Gag-PKB led to an increase in Glut 4 myc amount at the cell surface. Our results suggest that PKB could play a role in promoting Glut 4 appearance at the cell surface following exposure of adipocytes to insulin and okadaic acid stimulation.


2021 ◽  
Vol 106 ◽  
pp. 104500
Author(s):  
Yuanren Ma ◽  
Tongxi Zhou ◽  
Ping Zhao ◽  
Ho-Young Choi ◽  
Ji Hao ◽  
...  

1994 ◽  
Vol 77 (4) ◽  
pp. 1597-1601 ◽  
Author(s):  
J. Gao ◽  
J. Ren ◽  
E. A. Gulve ◽  
J. O. Holloszy

The maximal effects of insulin and muscle contractions on glucose transport are additive. GLUT-4 is the major glucose transporter isoform expressed in skeletal muscle. Muscle contraction and insulin each induce translocation of GLUT-4 from intracellular sites into the plasma membrane. The purpose of this study was to test the hypothesis that the incremental effect of contractions and insulin on glucose transport is mediated by additivity of the maximal effects of these stimuli on GLUT-4 translocation into the sarcolemma. Anesthetized rats were given insulin by intravenous infusion to raise plasma insulin to 2,635 +/- 638 microU/ml. The gastrocnemius-plantaris-soleus group was stimulated to contract via the sciatic nerve by using a protocol that maximally activates glucose transport. After treatment with insulin, contractions, or insulin plus contractions or no treatment, the gastrocnemius-plantaris-soleus muscle group was dissected out and was subjected to subcellular fractionation to separate the plasma membrane and intracellular membrane fractions. Insulin induced a 70% increase and contractions induced a 113% increase in the GLUT-4 content of the plasma membrane fraction. The effects of insulin and contractions were additive, as evidenced by a 185% increase in the GLUT-4 content of the sarcolemmal fraction. This finding provides evidence that the incremental effect of maximally effective insulin and contractile stimuli on glucose transport is mediated by additivity of their effects on GLUT-4 translocation into the sarcolemma.


1998 ◽  
Vol 274 (5) ◽  
pp. R1446-R1453 ◽  
Author(s):  
T. S. David ◽  
P. A. Ortiz ◽  
T. R. Smith ◽  
J. Turinsky

Rat epididymal adipocytes were incubated with 0, 0.1, and 1 mU sphingomyelinase/ml for 30 or 60 min, and glucose uptake and GLUT-1 and GLUT-4 translocation were assessed. Adipocytes exposed to 1 mU sphingomyelinase/ml exhibited a 173% increase in glucose uptake. Sphingomyelinase had no effect on the abundance of GLUT-1 in the plasma membrane of adipocytes. In contrast, 1 mU sphingomyelinase/ml increased plasma membrane content of GLUT-4 by 120% and produced a simultaneous decrease in GLUT-4 abundance in the low-density microsomal fraction. Sphingomyelinase had no effect on tyrosine phosphorylation of either the insulin receptor β-subunit or the insulin receptor substrate-1, a signaling molecule in the insulin signaling pathway. It is concluded that the incubation of adipocytes with sphingomyelinase results in insulin-like translocation of GLUT-4 to the plasma membrane and that this translocation does not occur via the activation of the initial components of the insulin signaling pathway.


1998 ◽  
Vol 6 (4) ◽  
pp. 224-227 ◽  
Author(s):  
J. M??ller-H??cker ◽  
A. Sch??fer ◽  
T. Strowitzki

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2599
Author(s):  
Thi-Ngoc-Mai Tran ◽  
Guillaume Bernadat ◽  
Dinh-Tri Mai ◽  
Van-Kieu Nguyen ◽  
Jirapast Sichaem ◽  
...  

Two new cycloartane glycosides, nervisides I–J, were isolated from Nervilia concolor whole plants. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data. These cycloartanes comprised a stereogenic center at C-24, the R configuration of which was assigned based on DFT-NMR calculations and the subsequent DP4 probability score. These compounds were tested for cytotoxicity against K562 and MCF-7 tumor cell lines, revealing mild cytotoxic activity.


2001 ◽  
Vol 86 (11) ◽  
pp. 5450-5456 ◽  
Author(s):  
Lidia Maianu ◽  
Susanna R. Keller ◽  
W. Timothy Garvey

Insulin resistance in type 2 diabetes is due to impaired stimulation of the glucose transport system in muscle and fat. Different defects are operative in these two target tissues because glucose transporter 4 (GLUT 4) expression is normal in muscle but markedly reduced in fat. In muscle, GLUT 4 is redistributed to a dense membrane compartment, and insulin-mediated translocation to plasma membrane (PM) is impaired. Whether similar trafficking defects are operative in human fat is unknown. Therefore, we studied subcellular localization of GLUT4 and insulin-regulated aminopeptidase (IRAP; also referred to as vp165 or gp160), which is a constituent of GLUT4 vesicles and also translocates to PM in response to insulin. Subcutaneous fat was obtained from eight normoglycemic control subjects (body mass index, 29 ± 2 kg/m2) and eight type 2 diabetic patients (body mass index, 30 ± 1 kg/m2; fasting glucose, 14 ± 1 mm). In adipocytes isolated from diabetics, the basal 3-O-methylglucose transport rate was decreased by 50% compared with controls (7.1 ± 2.9 vs. 14.1 ± 3.7 mmol/mm2 surface area/min), and there was no increase in response to maximal insulin (7.9 ± 2.7 vs. 44.5 ± 9.2 in controls). In membrane subfractions from controls, insulin led to a marked increase of IRAP in the PM from 0.103 ± 0.04 to 1.00± 0.33 relative units/mg protein, concomitant with an 18% decrease in low-density microsomes and no change in high-density microsomes (HDM). In type 2 diabetes, IRAP overall expression in adipocytes was similar to that in controls; however, two abnormalities were observed. First, in basal cells, IRAP was redistributed away from low-density microsomes, and more IRAP was recovered in HDM (1.2-fold) and PM (4.4-fold) from diabetics compared with controls. Second, IRAP recruitment to PM by maximal insulin was markedly impaired. GLUT4 was depleted in all membrane subfractions (43–67%) in diabetes, and there was no increase in PM GLUT4 in response to insulin. Type 2 diabetes did not affect the fractionation of marker enzymes. We conclude that in human adipocytes: 1) IRAP is expressed and translocates to PM in response to insulin; 2) GLUT4 depletion involves all membrane subfractions in type 2 diabetes, although cellular levels of IRAP are normal; and 3) in type 2 diabetes, IRAP accumulates in membrane vesicles cofractionating with HDM and PM under basal conditions, and insulin-mediated recruitment to PM is impaired. Therefore, in type 2 diabetes, adipocytes express defects in trafficking of GLUT4/IRAP-containing vesicles similar to those causing insulin resistance in skeletal muscle.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1936
Author(s):  
Kobina Essandoh ◽  
Shan Deng ◽  
Xiaohong Wang ◽  
Yutian Li ◽  
Qianqian Li ◽  
...  

Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I/R hearts which in turn, attenuation of I/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease.


2019 ◽  
Vol 12 (5) ◽  
pp. 684-688
Author(s):  
Bambang Purwanto ◽  
Sundari Indah Wiyasihati ◽  
Putri Ayu Masyitha ◽  
Kristanti Wanito Wigati ◽  
Irfiansyah Irwadi

Background: Streptozotocin (STZ)-induced free radical oxidant activity resulted in muscle wasting due to protein carbonyl (PC), glucose transporter-4 (Glut-4), and interleukin-6 (IL-6) protein alteration. Antioxidant ingredient in the golden sea cucumber extract was found in promising level to inhibit free radical activity. Aim: This study was aimed to investigate the effect of golden sea cucumber extract on PC, IL-6, and Glut-4 level of STZ-induced diabetes mouse. Materials and Methods: This study was performed using mice, which were grouped into non-diabetes, diabetes, and diabetes-treated extract groups. The golden sea cucumber was extracted using 70% ethanol, which was administered by oral gavage twice a day for 5 consecutive days. Results: The extract reduced PC level and improved muscle Glut-4 and IL-6 protein level of diabetic mouse. Conclusion: The extract of golden sea cucumber revived muscle Glut-4 and IL-6 protein level in protection against muscle wasting.


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