Submitted on May 16, 2006
Accepted on July 18, 2006
Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase
Jeong-Sun Ju1, Michael A. Gitcho1, Carter A. Casmaer1, Pankaj B. Patil1, Dae-Gyue Han1, Susan A. Spencer1, and Jonathan S Fisher2*
1 Department of Biology, Saint Louis University, St. Louis, Missouri, United States
2 Department of Biology, Saint Louis University, Room 128 Macelwane Hall, St Louis, Missouri, 63103, United States
* To whom correspondence should be addressed. E-mail: fisherjs{at}slu.edu.
Data from the use of activators and inhibitors of the AMP-activated protein kinase (AMPK) suggest that AMPK increases sensitivity of glucose transport to stimulation by insulin in muscle cells. We assayed insulin action after adenoviral transduction of constitutively active (Ad-AMPK-CA, a truncated form of AMPK
1) and dominant negative (Ad-AMPK-DN, that depletes endogenous AMPK) forms of AMPK into C2C12 myotubes. Compared with control (Ad-GFP), Ad-AMPK-CA increased the ability of insulin to stimulate glucose transport. The increased insulin action in cells expressing AMPK-CA was suppressed by Compound C (an AMPK inhibitor). Exposure of cells to AICAR (an AMPK activator) increased insulin action in uninfected myotubes and myotubes transduced with GFP but did not increase insulin action in Ad-AMPK-DN myotubes. Ad-AMPK-CA transduced cells had decreased serine phosphorylation of IRS-1 at an mTOR (or SK6) target site that is reportedly associated with insulin resistance. These data suggest that in myotubes, activated AMPK1 is sufficient to increase insulin action and that presence of functional AMPK is necessary to AICAR-related increases in insulin action.
