Insulin-Stimulated Phosphatidylinositol 3-Kinase Activity and 2-Deoxy-D-Glucose Uptake in Rat Skeletal Muscles

Elmendorf, Jeffrey S.; Damrau-Abney, Alice; Smith, T.; David, Tonya S.; Turinsky, J.

doi:10.1006/bbrc.1995.1453

Cited by 26 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is contrary to what was seen in cell culture, a phenomena that may result from the reported differential effects of PX-866 in 2-D and 3-D cultures (31), or the well established relationship between PI-3-kinase signaling and angiogenesis (32). Pioglitazone increased the uptake of glucose by normal tissue, presumably muscle and adipose tissue which are known to take up glucose in response to insulin (33). PX-866 showed a small inhibition of glucose uptake by normal tissue by itself, and reversed the increase by pioglitazone to values that were the same as in untreated animals.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Ihle

Lemos

Schwartz

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. The peroxisome proliferator-activated receptor ; agonist pioglitazone, used to treat type 2 diabetes, prevents a decrease in glucose tolerance caused by acute administration of PX-866. Our studies have shown that pioglitazone does not inhibit the antitumor activity of PX-866 in A-549 non-small cell lung cancer and HT-29 colon cancer xenografts. In vitro studies also showed that pioglitazone increases 2-[1-14 C]deoxy-Dglucose uptake in L-6 muscle cells and prevents inhibition of 2-deoxyglucose uptake by PX-866. Neither pioglitazone nor PX-866 had an effect on 2-deoxyglucose uptake in A-549 lung cancer cells. In vivo imaging studies using [ 18

show abstract

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Ihle

Lemos

Schwartz

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Then the regulatory subunit of phosphatidylinositol 3-kinase (p85) binds to a tyrosine-phosphorylated src homology binding domain on IRS-1, and this, in turn, increases the activity of the catalytic (pi 10) subunit of phosphatidylinositol 3-kinase (Kahn et al 1993). Studies with wortmannin, an inhibitor of phosphatidylinositol 3-kinase, support the notion that phosphatidylinos¬ itol 3-kinase is a part of the transduction pathway which effects the insulin-induced stimulation of glucose uptake in adipocytes (Okada et al 1994) and skeletal muscle (Elmendorf et al 1995, Yeh et al 1995. Phosphatidyl¬ inositol 3-kinase appears to be involved only in stimulation of glucose uptake by insulin, because wortmannin does not inhibit augmentation of muscle glucose uptake by contrac¬ tions and hypoxia (Yeh et al 1995) or by sphingomyelinase (Turinsky et al 1996).…”

Section: Introductionmentioning

confidence: 87%

“…Available evidence suggests that phosphatidylinositol 3-kinase is a part of the transduction pathway which effects the stimulation of glucose uptake by insulin. Inhibition of phosphatidyl¬ inositol 3-kinase with wortmannin has been shown to inhibit augmentation of muscle glucose uptake caused by insulin (Elmendorf et al 1995, Yeh et al 1995 but not by hypoxia or contractions (Yeh et al 1995).…”

Section: Role Of Atpmentioning

confidence: 97%

“…To verify this observation, the effect of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, on monensin-induced increase in basal 2-deoxyglucose uptake was examined. The concentration of wortmannin used in this study was the concentration which in our hands inhibits insulin-stimulated increase in 2-deoxyglucose uptake by muscle (Elmendorf et al 1995).…”

Section: Role Of Atpmentioning

confidence: 99%

See 1 more Smart Citation

Effect of monensin on 2-deoxyglucose uptake, the insulin receptor and phosphatidylinositol 3-kinase activity in rat muscle

Turinsky

Damrau-Abney

Elmendorf

et al. 1997

Journal of Endocrinology

View full text Add to dashboard Cite

Preincubation of rat soleus muscle with 1 and 10 microM monensin for 2 h increased the subsequent basal 2-deoxyglucose uptake by muscle 76 and 121% respectively. Under the same conditions, monensin decreased the insulin-stimulated (1 mU/ml) 2-deoxyglucose uptake by 29 and 37% respectively. The monensin-induced augmentation of basal 2-deoxyglucose uptake was inhibited 92% by cytochalasin B suggesting that the uptake is mediated by glucose transporters. Monensin did not increase the cellular accumulation of L-glucose in muscle indicating that it does not affect the cell membrane integrity. Neither the stimulatory effect of monensin on basal 2-deoxyglucose uptake nor the opposite, inhibitory action of monensin on the insulin-stimulated 2-deoxyglucose uptake were influenced by the removal of Ca2+ from the medium or by dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, suggesting that the actions of monensin are not mediated by calcium. Monensin had no effect on muscle ATP concentration. The monensin-induced augmentation of basal 2-deoxyglucose uptake was neither associated with stimulation of muscle phosphatidylinositol 3-kinase activity nor inhibited by wortmannin, demonstrating that the increase in basal 2-deoxyglucose uptake is not mediated by activation of phosphatidylinositol 3-kinase. The inhibition of insulin-stimulated 2-deoxyglucose uptake by monensin was associated with a 31% decrease in the abundance of insulin receptors in muscles, a 64% decrease in the insulin-induced autophosphorylation of the insulin receptor beta-subunit, and a 44% reduction of the insulin-stimulated phosphatidylinositol 3-kinase activity. Addition of monensin into the phosphatidylinositol 3-kinase reaction had no effect on the activity of the enzyme, demonstrating that the inhibition in monensin-treated muscles is indirect and occurs upstream of phosphatidylinositol 3-kinase. It is concluded that monensin has a dual effect on 2-deoxyglucose uptake by skeletal muscle: it stimulates basal uptake but inhibits the insulin-stimulated uptake. The primary cause of the latter, inhibitory effect of monensin is at the level of the insulin receptor.

show abstract

“…Then the study investigated whether pycnogenol ® stimulates phosphorylation and activates tyrosine kinase, which in turn would phosphorylate and activate Akt primarily through the PI3K-dependent pathway. It was recently reported that PI3K was a major site of peripheral tissue resistance to insulin in diabetes (Elmendorf et al, 1995). Second, it was confi rmed that…”

Section: Confl Ict Of Interestmentioning

confidence: 98%

Effect of pycnogenol^® on glucose transport in mature 3T3‐L1 Adipocytes

Lee

Kim

Lee

et al. 2010

Phytotherapy Research

View full text Add to dashboard Cite

Pycnogenol, a procyanidins-enriched extract of Pinus maritima bark, possesses antidiabetic properties, which improves the altered parameters of glucose metabolism that are associated with type 2 diabetes mellitus (T2DM). Since the insulin-stimulated antidiabetic activities of natural bioactive compounds are mediated by GLUT4 via the phosphatidylinositol-3-kinase (PI3K) and/or p38 mitogen activated protein kinase (p38-MAPK) pathway, the effects of pycnogenol were examined on the molecular mechanism of glucose uptake by the glucose transport system. 3T3-L1 adipocytes were treated with various concentrations of pycnogenol, and glucose uptake was examined using a non-radioisotope enzymatic assay and by molecular events associated with the glucose transport system using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results show that pycnogenol increased glucose uptake in fully differentiated 3T3-L1 adipocytes and increased the relative abundance of both GLUT4 and Akt mRNAs through the PI3K pathway in a dose dependent manner. Furthermore, pycnogenol restored the PI3K antagonist-induced inhibition of glucose uptake in the presence of wartmannin, an inhibitor of the PI3K. Overall, these results indicate that pycnogenol may stimulate glucose uptake via the PI3K dependent tyrosine kinase pathways involving Akt. Further the results suggest that pycnogenol might be useful in maintaining blood glucose control.

show abstract

Insulin-Stimulated Phosphatidylinositol 3-Kinase Activity and 2-Deoxy-D-Glucose Uptake in Rat Skeletal Muscles

Cited by 26 publications

References 0 publications

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Effect of monensin on 2-deoxyglucose uptake, the insulin receptor and phosphatidylinositol 3-kinase activity in rat muscle

Effect of pycnogenol^® on glucose transport in mature 3T3‐L1 Adipocytes

Contact Info

Product

Resources

About

Insulin-Stimulated Phosphatidylinositol 3-Kinase Activity and 2-Deoxy-D-Glucose Uptake in Rat Skeletal Muscles

Cited by 26 publications

References 0 publications

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity

Effect of monensin on 2-deoxyglucose uptake, the insulin receptor and phosphatidylinositol 3-kinase activity in rat muscle

Effect of pycnogenol® on glucose transport in mature 3T3‐L1 Adipocytes

Contact Info

Product

Resources

About

Effect of pycnogenol^® on glucose transport in mature 3T3‐L1 Adipocytes