title: Regulation of initiation of protein synthesis by insulin in skeletal muscle.
abstract: Protein synthesis is impaired in skeletal muscle and heart from diabetic rats. In muscles composed primarily of slow-twitch fibres (e.g. heart or soleus), the inhibition of protein synthesis can be accounted for entirely by a decrease in the amount of RNA. In contrast, in muscles of mixed fibre composition (e.g. gastrocnemius or psoas), the inhibition of protein synthesis is associated with an impairment in peptide-chain initiation. We have found that the inhibition of peptide-chain initiation that occurs in muscles composed of mixed fast-twitch fibres involves eukaryotic initiation factor 2B (eIF-2B). Thus, eIF-2B activity is inhibited in gastrocnemius and psoas but not heart or soleus from diabetic rats. In other systems eIF-2B activity is regulated by phosphorylation of the alpha-subunit of a second initiation factor, eIF-2. However, we have found no change in the phosphorylation state of eIF-2 alpha in either fast- or slow-twitch muscles from diabetic compared to control animals. Instead, the available evidence suggests that eIF-2B activity may be modulated by an alternate mechanism such as a change in the extent of phosphorylation of the 82,000 Mr subunit of the factor or a change in the NADPH/NADP+ ratio.
authors.affiliation: Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033.
authors.forename: S R
authors.initials: SR
authors.lastname: Kimball
authors.forename: L S
authors.initials: LS
authors.lastname: Jefferson
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000502:physiology*; D009132:Muscles / Q000378:metabolism*; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics
chemical_list: D007328:Insulin; D011506:Proteins