INCREASED RATES OF DUODENAL MUCOSAL PROTEIN-SYNTHESIS IN-VIVO IN PATIENTS WITH UNTREATED CELIAC-DISEASE

Background and Aims-A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to inv estigate possible differences between the rate of duodenal mucosal pro tein synthesis in coeliac patients and normal control subjects. Patien ts and Methods-Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven c ontrol subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received pr imed, continuous, intragastric (IG) and intravenous (IV) infusions of L-[1-C-13]leucine and L-[1-C-13]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements. Results-Rates of duodena l protein synthesis were significantly greater in coeliac patients tha n in control subjects (IV tracer, coeliac v control, 3.58 (0.45) v 2.2 6 (0.22)%/h, p<0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectiv ely, p<0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protei n/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/mu g v 13.0 (2.2) mg/mu g respectively, p<0.05) suggesting smaller mucosal cell size in coeliac patients. Conclusions -Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably incr eased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.