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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 …