Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity

被引:62
作者
Luzi, L
Castellino, P
DeFronzo, RA
机构
[1] UNIV TEXAS, CTR HLTH SCI, DEPT MED, DIABET DIV, SAN ANTONIO, TX 78284 USA
[2] AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA
[3] IST SCI SAN RAFFAELE, DEPT INTERNAL MED, RADIOACT & STABLE ISOTOPES LAB, I-20132 MILAN, ITALY
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1996年 / 270卷 / 02期
关键词
insulin resistance; amino acids; protein synthesis; proteolysis;
D O I
10.1152/ajpendo.1996.270.2.E273
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Seven normal glucose-tolerant obese subjects [ideal body weight (IBW) = 161%] and 18 controls (IBW = 102%) were studied with the euglycemic insulin damp (10 and 40 mU . m(-2). min(-1)) technique, [C-14]leucine infusion, and indirect calorimetry to examine if the insulin resistance with respect to glucose metabolism extends to amino acid/protein metabolism. In the basal state, total plasma amino acid and leucine concentrations, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) were similar in obese and control subjects. During both low (10 mU . m(-2). min(-1))- and higher (40 mU . m(-2). min(-1))-dose insulin clamp studies, insulin-mediated glucose uptake was reduced in obese vs. control subjects (P < 0.01). During the last hour of the higher-dose insulin clamp step, the decrease in total plasma amino acids, branched-chain amino acids, and leucine concentration was impaired in obese vs. control subjects (P < 0.01). However, suppression of ELF and NOLD was similar in both groups. During the low-dose insulin clamp, the decrease in plasma leucine concentration, LO, and ELF all were impaired (P < 0.01). A second study was performed in which the total plasma amino acid concentration was increased two- to threefold in both groups. Under these conditions of low plasma insulin/high amino acid levels, LO and NOLD increased similarly in obese and control subjects. In conclusion, insulin resistance is a common feature of both glucose and protein metabolism in obesity. The defect in protein metabolism is characterized by an impairment of the ability of insulin to inhibit proteolysis; the stimulatory effect of hyperaminoacidemia on protein synthesis is intact in obesity.
引用
收藏
页码:E273 / E281
页数:9
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