title: Insulin-stimulated plasma membrane association and activation of Akt2, aPKC zeta and aPKC lambda in high fat fed rodent skeletal muscle.
abstract: Several recent reports using cell lines have suggested that both Akt and atypical protein kinase C (aPKC) zeta/lambda are translocated to the plasma membrane (PM) in response to insulin. However, it has yet to be determined in skeletal muscle whether: (1) insulin increases PM-associated Akt2, aPKC zeta and/or lambda protein concentration, (2) the activity of these kinases is altered by insulin at the PM, and (3) high fat feeding alters the insulin-stimulated PM concentration and/or activity of Akt2 and aPKC zeta/lambda. Sprague-Dawley rats were randomly assigned to either normal (n=16) or high fat (n=16) dietary groups. Following a 12 week dietary period, animals were subjected to hind limb perfusions in the presence (n=8 per group) or absence (n=8 per group) of insulin. In normal skeletal muscle, total PI3-kinase, Akt2 and aPKC zeta/lambda activities were increased by insulin. PM-associated aPKC zeta and lambda, and aPKC zeta/lambda activity, but not Akt2 or Akt2 activity, were increased by insulin in normal muscle. High fat feeding did not alter total skeletal muscle Akt2, aPKC zeta or aPKC lambda protein concentration. Insulin-stimulated total PI3-kinase, Akt2 and aPKC zeta/lambda activities were reduced in the high fat fed animals. Insulin-stimulated PM aPKC zeta, aPKC lambda, aPKC zeta/lambda activity and GLUT4 protein concentration were also reduced in high fat fed animals. These findings suggest that in skeletal muscle, insulin stimulates translocation of aPKC zeta and lambda, but not Akt2, to the PM. In addition, high fat feeding impairs insulin-stimulated activation of total aPKC zeta/lambda and Akt2, as well as PM association and activation of aPKC zeta and lambda.
authors.affiliation: Department of Kinesiology, California State University Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8287, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Herr
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bernard
authors.forename: Donald W
authors.initials: DW
authors.lastname: Reeder
authors.forename: Donato A
authors.initials: DA
authors.lastname: Rivas
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Limon
authors.forename: Ben B
authors.initials: BB
authors.lastname: Yaspelkis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D004041:Dietary Fats / Q000494:pharmacology; D004822:Epididymis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D004041:Dietary Fats; D005947:Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007527:Isoenzymes; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta; C526296:Irs1 protein, rat; C495694:Slc2a4 protein, rat; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat