Effects of vitamin D metabolites on protein catabolism of muscle from uremic rats

H. R. Harter, S. J. Birge, K. J. Martin, S. Klahr, I. E. Karl

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Abstract

Epitrochlearis muscles obtained from normal male Sprague-Dawley rats used as controls (C) and rats with reduced renal mass (Nx) were incubated for 1 hr in Krebs-Ringer buffer containing 5 mM glucose with or without insulin. 25-hydroxycholecalciferol [25(OH)D3] or 1,25 dihydroxycholecalciferol [1,25(OH)2D3]. Plasma levels of 25(OH)D3 wwere unaffected by reduction in renal mass. Alanine (ALA), tyrosine (TYR), and phenylalanine (PHE) release rates from muscles of Na rats were increased 40% above C values. Addition of 100 ng/ml of 25(OH)D3 to the incubating media reduced these release rates to C values within 1 hr of incubation. No additive effects with insulin were seen. Addition of 1 ng/ml of 1,25(OH)2D3 did not effect these results. Reduction of renal mass or the addition of insulin or 25(OH)D3 did not effect tissue concentrations of ATP or phosphocreatine. On the other hand, tissue levels of TYR and PHE were increased significantly (≃ 20 to 25%) in muscles from Nx rats compared to C values and were reduced to control values by the addition of 25(OH)D3. The addition of insulin to the incubating media reduced the tissue levels of TYR and PHE in muscles of C rats by ≃ 20%, but reduced these levels in muscles of Nx rats by ≃ 55%, 25(OH)D3 did not affect tissue levels of cyclic AMP in muscles from either C or Nx rats. Protein synthetic rates were reduced significantly in muscles fom Nx rats and returned to C values after 2 hr of incubation but were unaffected by 25(OH)D3. Muscle uptake of 3H,25(OH)D3 was reduced by ≃ 30% in muscles from Nx rats compared to C rats. These data suggest that increased muscle protein catabolism exists in rats with reduced renal mass which can be reduced to C values by 25(OH)D3 and does not appear to be mediated through stimulation of adenylate cyclase. 25(OH)D3 did not affect muscle protein synthetic rates. Reduced uptake of 3H,25(OH)D3 by muscles of Nx rats suggests that resistance of this vitamin metabolite may exist at the level of muscle in uremia.

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalUnknown Journal
Volume23
Issue number3
DOIs
StatePublished - Jan 1 1983

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    Harter, H. R., Birge, S. J., Martin, K. J., Klahr, S., & Karl, I. E. (1983). Effects of vitamin D metabolites on protein catabolism of muscle from uremic rats. Unknown Journal, 23(3), 465-472. https://doi.org/10.1038/ki.1983.43