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Articles in PresS, published online ahead of print October 8, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00020.2002
Submitted on January 22, 2002
Accepted on September 10, 2002
1 Department of Medicine, Istituto Scientifico H San Raffaele, MIlano, MI, Italy; DiSTAM, Universita degli Studi di Milano, Milano, MI, Italy
2 Department of Medicine, Istituto Scientifico H San Raffaele, MIlano, MI, Italy;
3 Department of Medicine, Istituto Scientifico H San Raffaele, MIlano, MI, Italy
4 Department of Neurosurgery, Istituto Scientifico H San Raffaele, Milano, MI, Italy
5 DiSTAM, Universita degli Studi di Milano, Milano, MI, Italy
6 Department of Medicine, Universita di Trieste, Trieste, MI, Italy
* To whom correspondence should be addressed. E-mail: battezzati.alberto{at}hsr.it.
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 effect of acromegaly and of its surgical cure on the insulin sensitivity of glucose and amino acid/protein metabolism were evaluated by infusing [6,6-2H2]glucose, [1-13C]leucine and [2-15N]glutamine during an euglycemic insulin (1mU/kg/min) clamp in 12 acromegalic patients, 6 studied again 6mos after successful adenomectomy and 8 healthy controls. Acromegalic patients, compared to post-surgical and control subjects, had higher postabsorptive glucose concentration (5.5±0.3 vs 4.9±0.2, p<0.05 and 5.1±0.1 µmol/l) and flux (2.7±0.1 vs 2.0±0.2, p<0.01 and 2.2±0.1, p<0.05, µmol/kg/min) 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 post-surgical 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 non-oxidative 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 post-surgical patients compared to -26±6%in controls, p<0.05). Within six months, surgery reverses insulin resistance for glucose but not for protein metabolism. After adenomectomy more leucine is oxidized during hyperinsulinemia.
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