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Full-Text Articles in Life Sciences

Pkd1 Inhibits Ampk2 Through Phosphorylation Of Serine 491 And Impairs Insulin Signaling In Skeletal Muscle Cells, Kimberly A. Coughlan, Rudy J. Valentine, Bella S. Sudit, Katherine Allen, Yossi Dagon, Barbara B. Kahn, Neil B. Ruderman, Asish K. Saha Apr 2019

Pkd1 Inhibits Ampk2 Through Phosphorylation Of Serine 491 And Impairs Insulin Signaling In Skeletal Muscle Cells, Kimberly A. Coughlan, Rudy J. Valentine, Bella S. Sudit, Katherine Allen, Yossi Dagon, Barbara B. Kahn, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

Background: Diminished activity of the enzyme AMP-activated protein kinase (AMPK) is associated with impaired insulin signaling.

Results: Protein Kinase (PK)C/D1 activation inhibits AMPK2 via Ser491 phosphorylation; PKD1 inhibition prevents this in skeletal muscle cells.

Conclusion: PKD1 is a novel upstream AMPK-kinase that phosphorylates AMPK on Ser491 and regulates insulin signaling.

Significance: PKD1 inhibition may be a novel strategy for improving insulin sensitivity.


Nutrient Excess And Ampk Downregulation In Incubated Skeletal Muscle And Muscle Of Glucose Infused Rats, Kimberly A. Coughlan, Thomas W. Balon, Rudy J. Valentine, Robert Petrocelli, Vera Schultz, Amana Brandon, Gregory J. Cooney, Edward W. Kraegen, Neil B. Ruderman, Asish K. Saha Apr 2019

Nutrient Excess And Ampk Downregulation In Incubated Skeletal Muscle And Muscle Of Glucose Infused Rats, Kimberly A. Coughlan, Thomas W. Balon, Rudy J. Valentine, Robert Petrocelli, Vera Schultz, Amana Brandon, Gregory J. Cooney, Edward W. Kraegen, Neil B. Ruderman, Asish K. Saha

Rudy Valentine

We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases occurring at 1 and 2h. The initial decrease in activity at 30min coincided with a significant increase in muscle glycogen. The subsequent decreases at 1h were ...


Imoxin Attenuates Lps‐Induced Inflammation And Murf1 Expression In Mouse Skeletal Muscle, Rudy J. Valentine, Matthew A. Jefferson, Marian L. Kohut, Hyeyoon Eo Mar 2019

Imoxin Attenuates Lps‐Induced Inflammation And Murf1 Expression In Mouse Skeletal Muscle, Rudy J. Valentine, Matthew A. Jefferson, Marian L. Kohut, Hyeyoon Eo

Rudy Valentine

The double‐stranded RNA‐dependent protein kinase (PKR) contributes to inflammatory cytokine expression and disease pathogenesis in many conditions. Limited data are available on the efficacy of the PKR inhibitor imoxin to prevent lipopolysaccharide (LPS)‐induced inflammation in skeletal muscle in vivo. The aim of this study was to evaluate the effect of imoxin, a PKR inhibitor, on inflammatory and atrophy signaling in skeletal muscle in response to an acute inflammatory insult with LPS. Six‐week old C57BL/6J mice received vehicle (saline) or 0.5 mg/kg imoxin 24 and 2 h prior to induction of inflammation via 1 ...


A Single High‐Fat Meal Alters Human Soluble Rage Profiles And Pbmc Rage Expression With No Effect Of Prior Aerobic Exercise, Kelly N.Z. Fuller, Rudy J. Valentine, Edwin R. Miranda, Prabhakaran Kumar, Bellur S. Prabhakar, Jacob M. Haus Mar 2019

A Single High‐Fat Meal Alters Human Soluble Rage Profiles And Pbmc Rage Expression With No Effect Of Prior Aerobic Exercise, Kelly N.Z. Fuller, Rudy J. Valentine, Edwin R. Miranda, Prabhakaran Kumar, Bellur S. Prabhakar, Jacob M. Haus

Rudy Valentine

A high‐fat diet can induce inflammation and metabolic diseases such as diabetes and atherosclerosis. The receptor for advanced glycation endproducts (RAGE) plays a critical role in metabolic disease pathophysiology and the soluble form of the receptor (sRAGE) can mitigate these effects. However, little is known about RAGE in the postprandial condition and the effect of exercise in this context. Thus, we aimed to determine the effects of a single high‐fat meal (HFM) with and without prior exercise on peripheral blood mononuclear cell (PBMC) RAGE biology. Healthy males (n = 12) consumed a HFM on two occasions, one without prior ...