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


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


RESULTS
During the early diabetic stage, IGF-I mRNA (0.430 +/- 0.031 vs 0.370 +/- 0.016 +/- 0.280 +/- 0.010, P < 0.01, < 0.001) and IGF-I peptide contents [(0.430 +/- 0.031) ng/mg vs (30.06 +/- 3.60 +/- 23.71 +/- 2.70) ng/mg, P < 0. 01, < 0.001] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetes. These parameters were further down regulated in diabetic rats with less duration of diabetes and non-diabetic control rats [IGF-I mRNA 0.320 +/- 0.021 - 0.230 +/- 0.060; IGF-I peptide (28.8 +/- 3.30 - 19.51 +/- 1.80) ng/mg]. They also correlated with nerve functional (sensory nerve conduction velocity: r = 0.714, P < 0.001, amplitude of evoked potentials: r = 0.716, P < 0.001, respectively) and structural abnormality (axonal size r = 0.81, P < 0.001) of the sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.


CONCLUSIONS
IGF-I gene expression in tissues was down-regulated from the early diabetic stage and the down-regulation varied with the severity and duration of diabetic state. The decrement in IGF-I level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.
Li
J
J
Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Wang
C
C
Chen
J
J
Li
X
X
Feng
Z
Z
Ma
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I