Peroxisome Proliferator-activated Receptor-γ Activation Enhances Insulin-stimulated Glucose Disposal by Reducing ped/pea-15 Gene Expression in Skeletal Muscle Cells

Ungaro, Paola; Mirra, Paola; Oriente, Francesco; Nigro, Cecilia; Ciccarelli, Marco; Vastolo, Viviana; Longo, Michele; Perruolo, Giuseppe; Spinelli, Rosa; Formisano, Pietro; Miele, Claudia; Béguinot, Francesco

doi:10.1074/jbc.m112.406637

Cited by 17 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, recent work from our group has shown over-expression of Ped/pea-15 mRNA in the tibialis skeletal muscle of C57Bl/6 mice in which obesity is induced by high fat (HFD) feeding [14]. We now report that the D4 treatment improves insulin sensitivity in HFD induced obese C57BL/6 mice, with no effect on the body weight of animals.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15

et al. 2013

Self Cite

View full text Add to dashboard Cite

Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1). Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4) restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15) by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

show abstract

Section: Discussionmentioning

confidence: 67%

“…Recent observation by Ungaro P. et al demonstrated that Ped/pea-15 mRNA expression is increased by 2-fold in the tibialis skeletal muscle tissue of 6 month old diet-induced obese C57BL/6 mice [14]. Therefore, we investigated if Ad-D4 may improve insulin sensitivity also in this model.…”

Section: Resultsmentioning

confidence: 89%

Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Real-time PCR analysis Total RNA extraction, cDNA synthesis and real-time PCR were performed as described in Ungaro et al [26]. Relative quantification of gene expression was calculated by the ΔΔC t method [27].…”

Section: Methodsmentioning

confidence: 99%

“…Western blot and nuclear extract preparation Cell lysis, nuclear extract preparation and western blot for protein expression analysis were performed as described in Ungaro et al [26] and Dignam et al [29]. Immunoblots were performed using primary antibodies for PREP1 (1:1000; # sc-25282 Santa Cruz Biotechnology, Dallas, TX, USA) and NF-κB p65 (1:1000; # sc-8008) and for phosphorylated 5′ AMPactivated protein kinase (pAMPK) (1:1000; # 2531 Cell Signaling Technology, Danvers, MA, USA) and AMPK (1:1000; # 2532 Cell Signaling Technology), with β-actin (1:1000; # sc-1616) or lamin A/C (1:1000; # sc-20681) as loading control.…”

Section: Methodsmentioning

confidence: 99%

Glucose-induced expression of the homeotic transcription factor Prep1 is associated with histone post-translational modifications in skeletal muscle

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rather, the epigenetic changes often modify chromatin structure and gene accessibility to the transcription machinery [2]. Thus, environmental factors may also epigenetically impact on genes which play an important role in the physiological control of glucose tolerance [3][4][5], even when these genes have not been recognized in previous genome-wide efforts or their function in energy homeostasis is indirect [6,7]. Similar to genetic polymorphisms [8], epigenetic modifications may alter the transcriptional activity of these genes and contribute to the insulin resistance, beta-cell and fat tissue dysfunction and type 2 diabetes phenotype, including response to anti-diabetic agents and occurrence of diabetes complications [9][10][11].…”

Section: Introductionmentioning

confidence: 98%

Understanding type 2 diabetes: from genetics to epigenetics

et al. 2015

Self Cite

View full text Add to dashboard Cite

The known genetic variability (common DNA polymorphisms) does not account either for the current epidemics of type 2 diabetes or for the family transmission of this disorder. However, clinical, epidemiological and, more recently, experimental evidence indicates that environmental factors have an extraordinary impact on the natural history of type 2 diabetes. Some of these environmental hits are often shared in family groups and proved to be capable to induce epigenetic changes which alter the function of genes affecting major diabetes traits. Thus, epigenetic mechanisms may explain the environmental origin as well as the familial aggregation of type 2 diabetes much easier than common polymorphisms. In the murine model, exposure of parents to environmental hits known to cause epigenetic changes reprograms insulin sensitivity as well as beta-cell function in the progeny, indicating that certain epigenetic changes can be transgenerationally transmitted. Studies from different laboratories revealed that, in humans, lifestyle intervention modulates the epigenome and reverts environmentally induced epigenetic modifications at specific target genes. Finally, specific human epigenotypes have been identified which predict adiposity and type 2 diabetes with much greater power than any polymorphism so far identified. These epigenotypes can be recognized in easily accessible white cells from peripheral blood, indicating that, in the future, epigenetic profiling may enable effective type 2 diabetes prediction. This review discusses recent evidence from the literature supporting the immediate need for further investigation to uncover the power of epigenetics in the prediction, prevention and treatment of type 2 diabetes.

show abstract

Peroxisome Proliferator-activated Receptor-γ Activation Enhances Insulin-stimulated Glucose Disposal by Reducing ped/pea-15 Gene Expression in Skeletal Muscle Cells

Cited by 17 publications

References 45 publications

Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15

Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15

Glucose-induced expression of the homeotic transcription factor Prep1 is associated with histone post-translational modifications in skeletal muscle

Understanding type 2 diabetes: from genetics to epigenetics

Contact Info

Product

Resources

About