Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic rats

• Published in: The American journal of physiology Vol. 264; no. 1; pp. E101 - E108
• Main Authors: Karinch, A.M, Kimball, S.R, Vary, T.C, Jefferson, L.S
• Format: Journal Article
• Language: English
• Published: United States 1993
• Subjects: Animals; casein; casein kinase ii; Casein Kinases; diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; enzyme activity; Eukaryotic Initiation Factor-2 - genetics; Eukaryotic Initiation Factor-2 - metabolism; Guanine Nucleotide Exchange Factors; kinases; Male; Muscle Proteins - biosynthesis; Muscles - metabolism; myocardium; Myocardium - metabolism; NADP (coenzyme); NADP - metabolism; NADP - pharmacology; Phosphorylation; Protein Kinases - metabolism; protein synthesis; Proteins - antagonists & inhibitors; Proteins - metabolism; Rats; Rats, Sprague-Dawley; Reference Values; RNA; RNA, Messenger - metabolism; skeletal muscle
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1993.264.1.E101

Peptide-chain initiation is inhibited in fast-twitch skeletal muscle, but not heart, of diabetic rats. We have investigated mechanisms that might maintain eukaryotic initiation factor (eIF)-2B activity, preventing loss of efficiency of protein synthesis in heart of diabetic rats but not in fast-twitch skeletal muscle. There was no change in the amount or phosphorylation state of eIF-2 in skeletal or cardiac muscle during diabetes. In contrast, eIF-2B activity was decreased in fast-twitch but not slow-twitch muscle from diabetic animals. NADP+ inhibited partially purified eIF-2B in vitro, but addition of equimolar NADPH reversed the inhibition. The NADPH-to-NADP+ ratio was unchanged in fast-twitch muscle after induction of diabetes but was increased in heart of diabetic rats, suggesting that NADPH also prevents inhibition of eIF-2B in vivo. The activity of casein kinase II, which can phosphorylate and activate eIF-2B in vitro, was significantly lower in extracts of fast-twitch, but not cardiac muscle, of diabetic rats compared with controls. The results presented here demonstrate that changes in eIF-2 alpha phosphorylation are not responsible for the effect of diabetes on eIF-2B activity in fast-twitch skeletal muscle. Modulation of casein kinase Il activity may be a factor in the regulation of protein synthesis in muscle during acute diabetes. The activity of eIF-2B in heart might be maintained by the increased NADPH/NADP+.