TY - JOUR

T1 - Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line

AU - Habinowski, Susan A.

AU - Hirshman, Michael

AU - Sakamoto, Kei

AU - Kemp, Bruce E.

AU - Gould, Stephen J.

AU - Goodyear, Laurie J.

AU - Witters, Lee A.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK to phosphorylate and inactivate aeetyl-CoA carboxylase (ACC), reducing malonyl-CoA formation. It has been suggested that AMPK may also regulate malonyl-CoA content by activation of malonyl-CoA decarboxylase (MCD). We have investigated the potential regulation of MCD by AMPK in exercising skeletal muscle, in an islet cell line, and in vitro. Three rat fast-twitch muscle types were studied using two different contraction methods or after exposure to the AMPK activator AICAR. Although all muscle treatments resulted in activation 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 in the activation of AMPK, namely low glucose and AICAR, also had no discernable effect on MCD activity. Last, AMPK did not phosphorylate in vitro either 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.

AB - The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK to phosphorylate and inactivate aeetyl-CoA carboxylase (ACC), reducing malonyl-CoA formation. It has been suggested that AMPK may also regulate malonyl-CoA content by activation of malonyl-CoA decarboxylase (MCD). We have investigated the potential regulation of MCD by AMPK in exercising skeletal muscle, in an islet cell line, and in vitro. Three rat fast-twitch muscle types were studied using two different contraction methods or after exposure to the AMPK activator AICAR. Although all muscle treatments resulted in activation 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 in the activation of AMPK, namely low glucose and AICAR, also had no discernable effect on MCD activity. Last, AMPK did not phosphorylate in vitro either 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.

KW - Acetyl-CoA carboxylase

KW - AMP-activated protein kinase

KW - Malonyl-CoA

KW - Malonyl-CoA decarboxylase

KW - Phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=0035580981&partnerID=8YFLogxK

U2 - 10.1006/abbi.2001.2589

DO - 10.1006/abbi.2001.2589

M3 - Journal article

C2 - 11716464

AN - SCOPUS:0035580981

VL - 396

SP - 71

EP - 79

JO - Nitric Oxide: Biology and Chemistry

JF - Nitric Oxide: Biology and Chemistry

SN - 1089-8603

IS - 1

ER -