Protein metabolism in glucagonoma

Although protein wasting and reduced amino acid concentrations are common f indings in glucagonoma patients, the mechanisms underlying these alteration s are unclear. Therefore, we studied basal postabsorptive leucine, phenylal anine and tyrosine turnover following L-[D-3]-Leucine. L-[D-5]-Phenylalanin e and L-[D-2]-Tyrosine i.v. infusions in one male and one female patient wi th glucagonoma, compared with healthy control volunteers. Plasma amino acid concentrations were reduced (-40 to 80 %, delta > 2 SD vs control subjects ) in both patients. Plasma leucine. phenylalanine and tyrosine rates of app earance in patients with glucagonoma were similar to values in the control subjects, except leucine rate of appearence in the female patient with gluc agonoma (+ approximate to 30%, delta > 2 SD). In contrast, the intracellula r leucine rate of appearence, reflecting protein degradation, was considera bly increased in both patients ( + 60-80 %. delta > 2 SD). Phenylalanine hy droxylation was moderately higher only in the male patient with glucagonoma (+ approximate to 30%, delta > 2 SD). Leucine, phenylalanine and tyrosine clearances (+ 100-300%). as well as phenylalanine hydroxylative clearance ( + 75-100%) were also increased in the patients. In conclusion, whole-body protein breakdown is enhanced in patients with glucagonoma compared with he althy control subjects. Phenylalanine hydroxylative clearance is also highe r. Reduced plasma amino acid concentrations are probably due, at least in p art, to their increased clearance. These alterations could contribute to th e determination of the catabolic state of the glucagonoma syndrome.