Battezzati Alberto, Benedini Stefano, Fattorini Annalisa, Losa Marco, Mortini Pietro, Bertoli Simona, Lanzi Roberto, Testolin Giulio, Biolo Gianni, Luzi Livio
Università degli Studi di Milano, 20131 Milan, Italy.
Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E823-9. doi: 10.1152/ajpendo.00020.2002. Epub 2002 Oct 8.
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.
肢端肥大症中的胰岛素抵抗会导致葡萄糖不耐受和糖尿病，但由于胰岛素和生长激素都能促进蛋白质积聚，所以其是否涉及蛋白质代谢尚不清楚。通过在12例肢端肥大症患者、6例成功进行腺瘤切除术后6个月再次接受研究的患者以及8名健康对照者中进行正常血糖胰岛素（1 mU·kg⁻¹·min⁻¹）钳夹试验期间输注[6,6-(²)H₂]葡萄糖、[1-(¹³)C]亮氨酸和[2-(¹⁵)N]谷氨酰胺，评估了肢端肥大症及其手术治愈对葡萄糖和氨基酸/蛋白质代谢胰岛素敏感性的影响。与术后和对照受试者相比，肢端肥大症患者的吸收后葡萄糖浓度更高（5.5±0.3 vs. 4.9±0.2 μmol/l，P<0.05，以及5.1±0.1 μmol/l）和通量（2.7±0.1 vs. 2.0±0.2 μmol·kg⁻¹·min⁻¹，P<0.01，以及2.2±0.1 μmol·kg⁻¹·min⁻¹，P<0.05），且胰岛素刺激的葡萄糖处置减少（与基础值相比，分别为+15±9 vs. +151±18%，P<0.01，以及219±58%，P<0.001）。各组间吸收后亮氨酸代谢相似。在肢端肥大症患者和术后受试者中，胰岛素对内源性亮氨酸通量的抑制作用小于对照组（-9±1和-12±2 vs. -18±2%，P<0.001和P<0.05），非氧化亮氨酸处置（-4±3和-1±3 vs. -18±2%，P<0.01和P<0.05），分别为蛋白水解和蛋白质合成的指标，以及亮氨酸氧化（术后患者为-17±6%，对照组为-26±6%，P<0.05）。在6个月内，手术可逆转葡萄糖的胰岛素抵抗，但不能逆转蛋白质代谢的胰岛素抵抗。腺瘤切除术后，高胰岛素血症期间更多的亮氨酸被氧化。
