Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity

被引:50
作者
Federici, M [1 ]
Porzio, O [1 ]
Lauro, D [1 ]
Borboni, P [1 ]
Giovannone, B [1 ]
Zucaro, L [1 ]
Hribal, ML [1 ]
Sesti, G [1 ]
机构
[1] Univ Roma Tor Vergata, Dipartimento Med Interna, Mol Med Lab, I-00173 Rome, Italy
关键词
D O I
10.1210/jc.83.8.2911
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.
引用
收藏
页码:2911 / 2915
页数:5
相关论文
共 24 条
  • [21] TREADWAY JL, 1989, J BIOL CHEM, V264, P21450
  • [22] INSULIN-LIKE GROWTH FACTOR-I RECEPTOR PRIMARY STRUCTURE - COMPARISON WITH INSULIN-RECEPTOR SUGGESTS STRUCTURAL DETERMINANTS THAT DEFINE FUNCTIONAL SPECIFICITY
    ULLRICH, A
    GRAY, A
    TAM, AW
    YANGFENG, T
    TSUBOKAWA, M
    COLLINS, C
    HENZEL, W
    LEBON, T
    KATHURIA, S
    CHEN, E
    JACOBS, S
    FRANCKE, U
    RAMACHANDRAN, J
    FUJITAYAMAGUCHI, Y
    [J]. EMBO JOURNAL, 1986, 5 (10) : 2503 - 2512
  • [23] HUMAN INSULIN-RECEPTOR AND ITS RELATIONSHIP TO THE TYROSINE KINASE FAMILY OF ONCOGENES
    ULLRICH, A
    BELL, JR
    CHEN, EY
    HERRERA, R
    PETRUZZELLI, LM
    DULL, TJ
    GRAY, A
    COUSSENS, L
    LIAO, YC
    TSUBOKAWA, M
    MASON, A
    SEEBURG, PH
    GRUNFELD, C
    ROSEN, OM
    RAMACHANDRAN, J
    [J]. NATURE, 1985, 313 (6005) : 756 - 761
  • [24] Valensise H, 1996, DIABETOLOGIA, V39, P952