The role of IGF-1 gene expression abnormality in pathogenesis of diabetic peripheral neuropathy.
OBJECTIVE
To explore the role of insulin-like growth factor 1 (IGF-1) gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.


METHODS
Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by revere transcriptase-polymer chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.


RESULTS
During early diabetic stage, IGF-1 mRNA [(0.430+/-0.031) vs. (0.370+/-0.016), P<0.01, (0.430+/-0.031) vs. (0.280+/-0.010), P<0.001, respectively], IGF-1 peptide contents [(38.44+/-3.60) ng/mg vs. (30.06+/-2.41) ng/mg, P<0.01, (38.44+/-3.6) ng/mg vs. (3.71+/-2.70) ng/mg P<0.001, respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0.320+/-0.021) to approximately (0.230+/-0.060); IGF-1 peptide (28.80+/-3.30) to approximately (19.51+/-1.80) ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity: r=0.741, P<0.001; amplitude of evoked potential: r=0.716, P<0.001, respectively) and structural abnormality (axonal area r=0.81, P<0.001) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.


CONCLUSIONS
IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.
Jianbo
Li
L
Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029.
Chengya
Wang
W
Jiawei
Chen
C
Xiaolu
Li
L
Zhenqing
Feng
F
Hongtai
Ma
M
D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism*; D004594:Electrophysiology; D005071:Evoked Potentials; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D000496:Alloxan