Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line

The AMP-activated protein kinase (AMPK) plays an important role in fuel met abolism in exercising skeletal muscle and possibly in the islet cell with r espect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMP K to phosphorylate and inactivate acetyl-CoA carboxylase (ACC), reducing ma lonyl-CoA formation. It has been suggested that AMPK may also regulate malo nyl-CoA content by activation of malonyl-CoA decarboxylase (MCD). We have i nvestigated the potential regulation of MCD by AMPK in exercising skeletal muscle, in an islet cell line, and in vitro. Three rat fast-twitch muscle t ypes were studied using two different contraction methods or after exposure to the AMPK activator AICAR. Although all muscle treatments resulted in ac tivation of AMPK and phosphorylation of ACC, no stimulus had any effect on MCD activity. In 832/13 INS-1 rat islet cells, two treatments that result i n the activation of AMPK, namely low glucose and AICAR, also had no discern able effect on MCD activity. Last, AMPK did not phosphorylate in vitro eith er recombinant MCD or MCD immunoprecipitated from skeletal muscle or heart. We conclude that MCD is not a substrate for AMPK in fast-twitch muscle or the 832/13 INS-1 islet cell line and that the principal mechanism by which AMPK regulates malonyl-CoA content is through its regulation of ACC. (C) 20 01 Elsevier Science.