title: Insulin action on protein metabolism in acromegalic patients.
abstract: Insulin resistance in acromegaly causes glucose intolerance and diabetes, but it is unknown whether it involves protein metabolism, since both insulin and growth hormone promote protein accretion. The effects of acromegaly and of its surgical cure on the insulin sensitivity of glucose and amino acid/protein metabolism were evaluated by infusing [6,6-(2)H(2)]glucose, [1-(13)C]leucine, and [2-(15)N]glutamine during a euglycemic insulin (1 mU x kg(-1) x min(-1)) clamp in 12 acromegalic patients, six studied again 6 mo after successful adenomectomy, and eight healthy controls. Acromegalic patients, compared with postsurgical and control subjects, had higher postabsorptive glucose concentration (5.5 +/- 0.3 vs. 4.9 +/- 0.2 micromol/l, P < 0.05, and 5.1 +/- 0.1 micromol/l) and flux (2.7 +/- 0.1 vs. 2.0 +/- 0.2 micromol x kg(-1) x min(-1), P < 0.01, and 2.2 +/- 0.1 micromol x kg(-1) x min(-1), P < 0.05) and reduced insulin-stimulated glucose disposal (+15 +/- 9 vs. +151 +/- 18%, P < 0.01, and 219 +/- 58%, P < 0.001 from basal). Postabsorptive leucine metabolism was similar among groups. In acromegalic and postsurgical subjects, insulin suppressed less than in controls the endogenous leucine flux (-9 +/- 1 and -12 +/- 2 vs. -18 +/- 2%, P < 0.001 and P < 0.05), the nonoxidative leucine disposal (-4 +/- 3 and -1 +/- 3 vs. -18 +/- 2%, P < 0.01 and P < 0.05), respectively, indexes of proteolysis and protein synthesis, and leucine oxidation (-17 +/- 6% in postsurgical patients vs. -26 +/- 6% in controls, P < 0.05). Within 6 mo, surgery reverses insulin resistance for glucose but not for protein metabolism. After adenomectomy, more leucine is oxidized during hyperinsulinemia.
authors.affiliation: Università degli Studi di Milano, 20131 Milan, Italy. battezzati.alberto@hsr.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Battezzati
authors.forename: Stefano
authors.initials: S
authors.lastname: Benedini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fattorini
authors.forename: Marco
authors.initials: M
authors.lastname: Losa
authors.forename: Pietro
authors.initials: P
authors.lastname: Mortini
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Lanzi
authors.forename: Giulio
authors.initials: G
authors.lastname: Testolin
authors.forename: Gianni
authors.initials: G
authors.lastname: Biolo
authors.forename: Livio
authors.initials: L
authors.lastname: Luzi
mesh_terms: D000172:Acromegaly / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D001823:Body Composition; D005260:Female; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007651:Keto Acids / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007328:Insulin; D007651:Keto Acids; D011506:Proteins; D005973:Glutamine; D019382:Human Growth Hormone; D007930:Leucine; D005947:Glucose