1.Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4.
Puttanarasaiah Mahesh KUMAR ; Marikunte V VENKATARANGANNA ; Kirangadur MANJUNATH ; Gollapalle L VISWANATHA ; Godavarthi ASHOK
Chinese Journal of Natural Medicines (English Ed.) 2014;12(12):895-900
The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro.
Biological Transport
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Dose-Response Relationship, Drug
;
Fruit
;
Gene Expression
;
drug effects
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Glucose
;
metabolism
;
Glucose Transporter Type 4
;
metabolism
;
Hypoglycemic Agents
;
pharmacology
;
In Vitro Techniques
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Insulin
;
metabolism
;
Momordica
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Muscle Fibers, Skeletal
;
drug effects
;
PPAR gamma
;
metabolism
;
Plant Extracts
;
pharmacology
;
Protein Biosynthesis
;
Protein Synthesis Inhibitors
;
pharmacology
;
Rosiglitazone
;
Thiazolidinediones
;
pharmacology
;
Up-Regulation
2.Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors
S DAUM ; J P MAGNUSSON ; L PES ; J GARCIA FERNANDEZ ; S CHERCHEJA ; F. MEDDA ; F I NOLLMANN ; S D KOESTER ; P PEREZ GALAN ; A WARNECKE ; K ABU AJAJ ; Felix KRATZ
Korean Journal of Nuclear Medicine 2019;53(3):189-198
PURPOSE:
The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors.
METHODS:
111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4–8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4–6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection.
RESULTS:
111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7–3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2–6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3–2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9–9.4.
CONCLUSION
111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.