The Mammalian Facilitative Glucose Transporter (GLUT) Family

Chen

BMC Complement Altern Med

2014

BackgroundRhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma β-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats).MethodsIn the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma β-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of β-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions.ResultsRhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid μ-receptors using cyprodime. An increase of plasma β-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid μ-receptors.ConclusionsTaken together, rhodiola-water extract improves hyperglycemia via an increase of β-endorphin secretion from adrenal gland to activate opioid μ-receptors in STZ-diabetic rats.

“…It has been reported that PKC is involved in the rate-limiting step in GLUT4 mRNA expression [54,55]. Also, the PLC–PKC pathway is mediated in opioid μ-receptor activation [20,44].…”

Section: Discussionmentioning

confidence: 99%

Antihyperglycemic action of rhodiola-aqeous extract in type1-like diabetic rats

Chen

BMC Complement Altern Med

2014

Journal of Pharmacy and Pharmacology

“…In this work we used ILC to investigate the effects of cholesterol and the transmembrane model proteins, the glucose transporter GLUT1 (Barrett et al 1999 ;Seatter & Gould 1999 ;Lagerquist Ha$ gglund et al 2000) and bacteriorhodopsin (Booth 2000 ;Krebs & Isenbarger 2000), on the partitioning of drugs into phospholipid bilayers and compared ILC data with drug permeabilities (P eff ). Various drugs which are well absorbed from the intestine were chosen to avoid the limitation inherent in analysis of homologous molecules and to confine the study to drugs taken up by the transcellular route.…”

Section: Introductionmentioning

confidence: 99%

Effects of cholesterol and model transmembrane proteins on drug partitioning into lipid bilayers as analysed by immobilized-liposome chromatography

Lagerquist

Beigi

Karlén

et al. 2001

We have analysed how cholesterol and transmembrane proteins in phospholipid bilayers modulate drug partitioning into the bilayers. For this purpose we determined the chromatographic retention of drugs on liposomes or proteoliposomes entrapped in gel beads. The drug retention per phospholipid amount (the capacity factor Ks) reflects the drug partitioning. Cholesterol in the bilayers decreased the Ks value and hence the partitioning into the membrane in proportion to the cholesterol fraction. On average this cholesterol effect decreased with increasing temperature. Model transmembrane proteins, the glucose transporter GLUT1 and bacteriorhodopsin, interacted electrostatically with charged drugs to increase or decrease the drug partitioning into the bilayers. Bacteriorhodopsin proteoliposomes containing cholesterol combined the effects of the protein and the cholesterol and approached the partitioning properties of red blood cell membranes. For positively charged drugs the correlation between calculated intestinal permeability and log Ks was fair for both liposomes and bacteriorhodopsin-cholesterol proteoliposomes. Detailed modeling of solute partitioning into biological membranes may require an extensive knowledge of their structures.

“…Despite our attempts to assess glucometabolic function in FLR with 18 F-FDG PET/CT imaging, a low level of GLUT1 expression in liver cells resulted in a continuous and low 18 F-FDG SUV max uptake in both the ALPPS and control animals. Thus, the pathophysiological mechanisms after the rst stage of ALPPS do not include accelerated glucometabolism relatated with GLUT1 in liver cells [36,37].…”

Section: Discussionmentioning

confidence: 99%

Determination of Pathophysiological Mechanisms of ALPPS in an Animal Model Using Molecular and Functional Imagings

Wang

Quan

Zheng

et al. 2020

Preprint

Background: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a two-stage strategy to induce rapid hypertrophy of future liver remnant (FLR) to increase hepatic tumor resectability and reduce postoperative liver failure rate. Rigorous and accurate determination of the pathophysiological mechanisms involved in hypertrophy of FLR in ALPPS is essential to ensure a good success rate in the second stage operation. Methods: An ALPPS model was established in rabbits with liver VX2 tumor. The pathophysiological mechanisms after the first stage of ALPPS in the FLR and tumor were assessed by multiplexed positron emission tomography (PET) tracers and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).Results: The tumor volume in the ALPPS model increased significantly from post-stage 1 ALPPS day 14 compared to control animals. The 18F-FDG uptake increased significantly from day 7 onwards in the ALPPS model. A Valid Volumetric Function measured by 18F-FCH showed good values in accurately monitoring dynamics and time window for functional liver regeneration (days 3 to 7). DCE-MRI revealed changes in the vascular hyperpermeability function, with a peak on day 7 for tumor and FLR. Conclusions: Molecular and functional imagings are promising and non-invasive methods to investigate the pathophysiological mechanisms of ALPPS with good potentials in clinical application to improve surgical successful outcomes.