scholarly journals Grape Seed-Derived Procyanidins Have an Antihyperglycemic Effect in Streptozotocin-Induced Diabetic Rats and Insulinomimetic Activity in Insulin-Sensitive Cell Lines

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4985-4990 ◽  
Author(s):  
M. Pinent ◽  
M. Blay ◽  
M. C. Bladé ◽  
M. J. Salvadó ◽  
L. Arola ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Cell Lines ◽  
Glucose Transporter ◽  
Insulin Dose ◽  
Grape Seed ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Sensitive Cell ◽  
Antihyperglycemic Effect ◽  
Altered Glucose

Abstract Flavonoids are functional constituents of many fruits and vegetables. Some flavonoids have antidiabetic properties because they improve altered glucose and oxidative metabolisms of diabetic states. Procyanidins are flavonoids with an oligomeric structure, and it has been shown that they can improve the pathological oxidative state of a diabetic situation. To evaluate their effects on glucose metabolism, we administered an extract of grape seed procyanidins (PE) orally to streptozotocin-induced diabetic rats. This had an antihyperglycemic effect, which was significantly increased if PE administration was accompanied by a low insulin dose. The antihyperglycemic effect of PE may be partially due to the insulinomimetic activity of procyanidins on insulin-sensitive cell lines. PE stimulated glucose uptake in L6E9 myotubes and 3T3-L1 adipocytes in a dose-dependent manner. Like insulin action, the effect of PE on glucose uptake was sensitive to wortmannin, an inhibitor of phosphoinositol 3-kinase and to SB203580, an inhibitor of p38 MAPK. PE action also stimulated glucose transporter-4 translocation to the plasma membrane. In summary, procyanidins have insulin-like effects in insulin-sensitive cells that could help to explain their antihyperglycemic effect in vivo. These effects must be added to their antioxidant activity to explain why they can improve diabetic situations.

Postreceptor defect in insulin action in streptozotocin-induced diabetic rats

1989 ◽  
Vol 256 (5) ◽  
pp. E624-E630 ◽  
Author(s):  
H. Nishimura ◽  
H. Kuzuya ◽  
M. Okamoto ◽  
K. Yamada ◽  
A. Kosaki ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Insulin Dose ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Maximal Response ◽  
Metabolic Clearance ◽  
Glucose Clamp Technique

To clarify the mechanism(s) responsible for the insulin resistance in streptozotocin (STZ)-treated diabetic rats, we studied insulin-induced glucose disposal by using the glucose clamp technique and measured insulin receptor and glucose transporter of muscles. The insulin dose-response curve of the metabolic clearance rate (MCR) of glucose revealed a decrease of the maximal response without a rightward shift in STZ rats. Maximal MCR was even lower when clamped at 300 rather than 150 mg/dl of blood glucose levels. Insulin binding to the crude plasma membrane of muscles from STZ rats was increased compared with controls. The number of glucose transporter of the plasma and microsomal membranes were significantly decreased in STZ rats. These in vivo and in vitro studies using skeletal muscles suggest that in STZ-treated diabetic rats 1) a defect or defects exist in the signal transduction mechanism of insulin in postbinding steps, 2) the decreased maximal MCR is related at least partly to the decrease of glucose transporter numbers, and 3) a defect in glucose metabolism (postglucose transport defect) is also present.

scholarly journals Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats

2017 ◽  
Vol 42 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Chika Ifeanyi Chukwuma ◽  
Md. Shahidul Islam
Keyword(s):  
Glycemic Control ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Glucose Absorption ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Intestinal Glucose Absorption ◽  
Type 2 Diabetic ◽  
Isolated Rat

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50= 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50= 3.5% ± 1.6%) or without insulin (GU50= 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

scholarly journals Insulin-regulated aminopeptidase inhibitors do not alter glucose handling in normal and diabetic rats

2017 ◽  
Vol 58 (4) ◽  
pp. 193-198 ◽  
Author(s):  
Anthony L Albiston ◽  
Mauricio Cacador ◽  
Puspha Sinnayah ◽  
Peta Burns ◽  
Siew Yeen Chai
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Specific Inhibitor ◽  
Diabetic Rats ◽  
Whole Body ◽  
Aminopeptidase Activity ◽  
Oral Glucose ◽  
Glucose Challenge

Insulin-regulated aminopeptidase (IRAP) co-localizes with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin-responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin-responsive cells. In both in vitro and in vivo studies, inhibition of IRAP aminopeptidase activity with the specific inhibitor, HFI-419, did not modulate glucose uptake. IRAP inhibition in the L6GLUT4myc cell line did not alter glucose uptake in both basal and insulin-stimulated state. In keeping with these results, HFI419 did not affect peripheral, whole-body glucose handling after an oral glucose challenge, neither in normal rats nor in the streptozotocin (STZ)-induced experimental rat model of diabetes mellitus (DM). Therefore, acute inhibition of IRAP aminopeptidase activity does not affect glucose homeostasis.

Di(2-ethylhexyl)phthalate exposure impairs insulin receptor and glucose transporter 4 gene expression in L6 myotubes

2013 ◽  
Vol 33 (7) ◽  
pp. 685-700 ◽  
Author(s):  
P Rajesh ◽  
K Balasubramanian
Keyword(s):  
Gene Expression ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Negative Influence ◽  
Receptor Protein ◽  
Dependent Manner ◽  
L6 Myotubes ◽  
Dose Dependent

Di(2-ethyl hexyl)-phthalate (DEHP) is an endocrine disrupter and is the most abundantly used phthalate derivative, which is suspected to be an inevitable environmental exposure contributing to the increasing incidence of type-2 diabetes in humans. Therefore, the present study was designed to address the dose-dependent effects of DEHP on insulin signaling molecules in L6 myotubes. L6 myotubes were exposed to different concentrations (25, 50, and 100 μM) of DEHP for 24 h. At the end of exposure, cells were utilized for assessing various parameters. Insulin receptor and glucose transporter4 (GLUT4) gene expression, insulin receptor protein concentration, glucose uptake and oxidation, and enzymatic and nonenzymatic antioxidants were significantly reduced, but glutamine fructose-6-phosphate amidotransferase, nitric oxide, lipid peroxidation, and reactive oxygen species levels were elevated in a dose-dependent manner in L6 myotubes exposed to DEHP. The present study in turn shows the direct adverse effect of DEHP on the expression of insulin receptor and GLUT4 gene, glucose uptake, and oxidation in L6 myotubes suggesting that DEHP exposure may have a negative influence on insulin signaling.

scholarly journals Myostatin regulates glucose uptake in BeWo cells

2007 ◽  
Vol 293 (5) ◽  
pp. E1296-E1302 ◽  
Author(s):  
Nisha Antony ◽  
John J. Bass ◽  
Christopher D. McMahon ◽  
Murray D. Mitchell
Keyword(s):  
Glucose Uptake ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Muscle Growth ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Bewo Cells ◽  
Placental Cells

Myostatin is a member of the transforming growth factor (TGF)-β superfamily, known for its ability to inhibit muscle growth. It can also regulate metabolism and glucose uptake in a number of tissues. To determine the mechanism of myostatin's effect on glucose uptake, we evaluated its actions using choriocarcinoma cell lines that are widely used as models for placental cells. Protein and mRNA were determined using immunoblotting and RT-PCR/PCR, respectively. Glucose uptake was assessed by uptake of radiolabeled deoxyglucose in vitro. All choriocarcinoma cell lines tested i.e., BeWo, JEG, and Jar, are used as models of placental cells, and all expressed myostatin protein and mRNA. Treatment of BeWo cells with myostatin resulted in inhibition of glucose uptake in a concentration-dependent manner ( P < 0.01). At all concentrations tested, follistatin, a functional inhibitor of myostatin, completely blocked the inhibitory effect of myostatin (40 nM) on glucose uptake by BeWo cells (0.4 nM, P < 0.05). Follistatin treatment alone also increased glucose uptake (0.4 and 4 nM, P < 0.001; 40 nM, P < 0.05). Because BeWo cells proliferated and greater cell densities were achieved, glucose uptake declined irrespective of treatment. Myostatin treatment of BeWo cells did not alter the levels of myostatin receptor, ActRII A/B proteins. The levels of glucose transport proteins also remained unaltered in BeWo cells with myostatin treatment. This study has shown that myostatin specifically inhibits glucose uptake into BeWo cells, suggesting that locally produced myostatin may control glucose metabolism within the placenta.

Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus

1994 ◽  
Vol 267 (5) ◽  
pp. F816-F824 ◽  
Author(s):  
R. G. Marcus ◽  
R. England ◽  
K. Nguyen ◽  
M. J. Charron ◽  
J. P. Briggs ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Experimental Diabetes Mellitus ◽  
Early Diabetes ◽  
Glut4 Expression ◽  
Microvascular Cells ◽  
Glucose Transporter Glut4

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.

scholarly journals Requirement of Atypical Protein Kinase Cλ for Insulin Stimulation of Glucose Uptake but Not for Akt Activation in 3T3-L1 Adipocytes

1998 ◽  
Vol 18 (12) ◽  
pp. 6971-6982 ◽  
Author(s):  
Ko Kotani ◽  
Wataru Ogawa ◽  
Michihiro Matsumoto ◽  
Tadahiro Kitamura ◽  
Hiroshi Sakaue ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Pleckstrin Homology Domain ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
Negative Effects ◽  
Stimulation Of

ABSTRACT Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation of glucose transport in adipocytes. Both Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, and atypical isoforms of protein kinase C (PKCζ and PKCλ) have been implicated as downstream effectors of PI 3-kinase. Endogenous or transfected PKCλ in 3T3-L1 adipocytes or CHO cells has now been shown to be activated by insulin in a manner sensitive to inhibitors of PI 3-kinase (wortmannin and a dominant negative mutant of PI 3-kinase). Overexpression of kinase-deficient mutants of PKCλ (λKD or λΔNKD), achieved with the use of adenovirus-mediated gene transfer, resulted in inhibition of insulin activation of PKCλ, indicating that these mutants exert dominant negative effects. Insulin-stimulated glucose uptake and translocation of the glucose transporter GLUT4 to the plasma membrane, but not growth hormone- or hyperosmolarity-induced glucose uptake, were inhibited by λKD or λΔNKD in a dose-dependent manner. The maximal inhibition of insulin-induced glucose uptake achieved by the dominant negative mutants of PKCλ was ∼50 to 60%. These mutants did not inhibit insulin-induced activation of Akt. A PKCλ mutant that lacks the pseudosubstrate domain (λΔPD) exhibited markedly increased kinase activity relative to that of the wild-type enzyme, and expression of λΔPD in quiescent 3T3-L1 adipocytes resulted in the stimulation of glucose uptake and translocation of GLUT4 but not in the activation of Akt. Furthermore, overexpression of an Akt mutant in which the phosphorylation sites targeted by growth factors are replaced by alanine resulted in inhibition of insulin-induced activation of Akt but not of PKCλ. These results suggest that insulin-elicited signals that pass through PI 3-kinase subsequently diverge into at least two independent pathways, an Akt pathway and a PKCλ pathway, and that the latter pathway contributes, at least in part, to insulin stimulation of glucose uptake in 3T3-L1 adipocytes.

Interleukin-1β Stimulates Glucose Uptake of Human Peritoneal Mesothelial Cells In Vitro

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 58-60 ◽  
Author(s):  
Michael Kruse ◽  
Arezki Mahiout ◽  
Volker Kliem ◽  
Peter Kurz ◽  
Karl-Martin Koch ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Interleukin 1 ◽  
Glucose Transporters ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells

To investigate whether the glucose uptake (GU) of human peritoneal mesothelial cells (HPMC) is mediated by glucose transporters and whether this uptake is influenced by interleukin 1–β (IL-1β), we measured 2-deoxy-(3H)-GU of HPMC in vitro, after exposing the cells for different times (two and 12 hours) to increasing concentrations (0.1, 1.0, and 2.0 ng/mL) of IL-1 β. To exclude a noncarrier-mediated transport, GU was also tested in the presence of cytochalasin B. All experiments were performed in triplicate in the cells of two donors. Cytochalasin B inhibits GU of HPMC almost completely. GU of HPMC is not stimulated by insulin. GU is stimulated by IL-1 β in a dose-dependent manner. These data indicate a GU of HPMC, which is mediated by a glucose transporter and stimulated by IL-1 β. The increased uptake of glucose from the dialysate In patients with peritonitis may be mediated by a (cytokineinduced) increased activity of HPMC glucose transporters.

scholarly journals Akt2-Dependent Beneficial Effect of Galanin on Insulin-Induced Glucose Uptake in Adipocytes of Diabetic Rats

2017 ◽  
Vol 41 (5) ◽  
pp. 1777-1787 ◽  
Author(s):  
Zhenwen Zhang ◽  
Penghua Fang ◽  
Lili Guo ◽  
Biao He ◽  
Mingyi Shi ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Diabetic Rats ◽  
Glucose Transporter 4 ◽  
Akt Inhibitor ◽  
Beneficial Effects ◽  
Forkhead Box

Background/Aims: Glucose uptake occurs via the activation of an insulin-signaling cascade, resulting in the translocation of glucose transporter 4 (GLUT4) to the plasma membrane of adipocytes and myocytes. Recent research found that galanin could boost insulin-induced glucose uptake. This study aimed to explore whether activation of Akt2 mediates the beneficial effects of galanin on insulin-induced glucose uptake in the adipocytes of diabetic rats. Method: In this experiment, insulin, galanin and MK-2206, an Akt inhibitor, were injected individually or in combination into diabetic rats once a day for ten days. Then, glucose uptake and pAkt2 and its downstream proteins were examined in adipocytes. Results: Administration of galanin significantly enhanced insulin-induced 2-Deoxy-D-[3H]glucose uptake; GLUT4 and vesicle-associated membrane protein 2 contents in plasma membranes; and pAkt2Thr308/Ser473 and Akt2 mRNA expression levels in adipocytes. In addition, Akt2 downstream proteins including phosphorylated AS160 were increased, but the levels of phosphorylated forkhead box O1 and glycogen synthase kinase-3β were reduced. Treatment with MK-2206 may block the beneficial effects of galanin on these insulin-induced events. Conclusions: The results of this study suggest that phosphorylation of Akt2 mediates the beneficial effects of galanin on insulin-induced glucose uptake in the adipocytes of diabetic rats.

scholarly journals The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2168 ◽  
Author(s):  
Reem T. Attia ◽  
Mai F. Tolba ◽  
Ruchit Trivedi ◽  
Mariane G. Tadros ◽  
Hossam M.M. Arafa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glucose Uptake ◽  
Cell Line ◽  
Cell Lines ◽  
Annexin V ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Lncap Cells ◽  
Caspase 9 ◽  
Glucosidase Activity

Background. Glufosfamide (GLU) is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to theβ-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects. The main objective of the current study is to assess the cytotoxic potential of GLU for the first time in prostate cancer (PC) cells representing different stages of the tumor. Furthermore, this study examined the potential synergistic activity of GLU in combination with docetaxel (DOC).Methods. Two different cell lines were used, LNCaP and PC-3. Concentration-response curves were assessed. The tested groups per cell line were, control, GLU, DOC and combination. Treatment duration was 72 h. Cytotoxicity was assessed using sulforhodamine B (SRB) assay and half maximal inhibitory concentration (IC50) was calculated. Synergy analyses were performed using Calcusyn®software. Subsequent mechanistic studies includedβ-glucosidase activity assay, glucose uptake and apoptosis studies, namely annexin V-FITC assay and the protein expression of mitochondrial pathway signals including Bcl-2, Bax, Caspase 9 and 3 were assessed. Data are presented as mean ± SD; comparisons were carried out using one way analysis of variance (ANOVA) followed by Tukey-Kramer’s test for post hoc analysis.Results. GLU induced cytotoxicity in both cell lines in a concentration-dependent manner. The IC50 in PC-3 cells was significantly lower by 19% when compared to that of LNCaP cells. The IC50 of combining both drugs showed comparable effect to DOC in PC-3 but was tremendously lowered by 49% compared to the same group in LNCaP cell line.β-glucosidase activity was higher in LNCaP by about 67% compared to that determined in PC-3 cells while the glucose uptake in PC-3 cells was almost 2 folds that found in LNCaP cells. These results were directly correlated to the efficacy of GLU in each cell line. Treatment of PC cells with GLU as single agent or in combination with DOC induced significantly higher apoptosis as evidenced by Annexin V-staining. Apoptosis was significantly increased in combination group by 4.9 folds and by 2.1 Folds when compared to control in LNCaP cells and PC-3 cells; respectively. Similarly, the expression of Bcl-2 was significantly decreased while Bax, caspase 9 and 3 were significantly increased in the combined treatment groups compared to the control.Conclusion. GLU has a synergistic effect in combination with DOC as it increases the cell kill which can be attributed at least partially to apoptosis in both the tested cell lines and it is suggested as a new combination regimen to be considered in the treatment of the prostate cancer. Further experiments and clinical investigations are needed for assessment of that regimen.

Sign in / Sign up

Export Citation Format

Share Document