Protein metabolism in clinically stable adult cystic fibrosis patients with abnormal glucose tolerance

Citation
A. Moran et al., Protein metabolism in clinically stable adult cystic fibrosis patients with abnormal glucose tolerance, DIABETES, 50(6), 2001, pp. 1336-1343
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
0012-1797 → ACNP
Volume
50
Issue
6
Year of publication
2001
Pages
1336 - 1343
Database
ISI
SICI code
0012-1797(200106)50:6<1336:PMICSA>2.0.ZU;2-5
Abstract
Cystic fibrosis (CF) patients are reported to experience chronic protein ca tabolism. Since diabetes or impaired glucose tolerance (IGT) is common in C F, me hypothesized that their protein catabolic state is related to reduced insulin secretion or reduced insulin action. A total of 12 clinically stab le adult CF patients with abnormal glucose tolerance and 12 age-, sex-, and lean body mass-matched healthy control subjects underwent protein turnover studies using L-[l-C-13]leucine, L-[N-15] phenylalanine, and L-[H-2(4)]tyr osine, with and without exogenous insulin infusion. In the baseline fasting state, protein metabolism was entirely normal in CF patients, with no evid ence of increased protein catabolism. In contrast, striking abnormalities m ere seen in CF patients when insulin was infused, since they did not experi ence normal suppression of the appearance rates of leucine, phenylalanine, or tyrosine (indexes of protein breakdown). At an insulin concentration of 45 +/- 2 muU/ml, normal control subjects suppressed the leucine appearance rate by 19 +/- 5% (P < 0.01), ketoisocaproate appearance rate by 10 <plus/m inus> 3% (P = 0.03), tyrosine appearance rate by 11 +/- 2% (P = 0.03), and phenylalanine appearance rate by 6 +/- 3% (P = 0.07). Phenylalanine convers ion to tyrosine decreased by 22 +/- 7% (P = 0.03). At a similar insulin con centration of 44 +/- 3 muU/ml, normal suppression of amino acid appearance did not occur in CF. The leucine appearance rate decreased by 4 +/- 2% (P = 0.65), ketoisocaproate appearance rate by 1 +/- 2% (P = 0.94), tyrosine ap pearance rate by 0 +/- 6% (P = 0.56), phenylalanine appearance rate by 5 +/ - 6% (P = 0.34), and phenylalanine conversion to tyrosine by 5 +/- 6% (P = 0.95). poor suppression of the amino acid appearance rate in CF was not rel ated to previously documented glucose tolerance status (IGT or CF-related d iabetes without fasting hyperglycemia), fasting insulin levels, the acute i nsulin response, insulin sensitivity, cytokine or counterregulatory hormone levels, resting energy expenditure, caloric intake, pulmonary function, or clinical status. Protein synthesis was not significantly affected by insul in infusion in either normal control subjects or CF patients. In conclusion , clinically stable adult CF patients have normal indexes of protein breakd own and synthesis in the fasting state. In contrast, elevation of plasma in sulin to physiological postprandial levels fails to normally suppress index es of protein breakdown. It is therefore likely that inability to spare pro tein during the postprandial state is the cause of protein catabolism in th ese patients.