Psychology of Movement Commons^™

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

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 …