NeuroscienceLetters, 113 (1990) 29-33
29
Elsevier Scientific Publishers Ireland Ltd.
N S L 06853
Conduction velocity of motor nerve and cervical sympathetic and vagus nerve in streptozotocin diabetic rats Y u k o Yamazaki, T a k e o Karakida and Shinji H o m m a Department of Physiology, Niigata UniversitySchoolof Medicine, Niigata (Japan) (Received I l December 1989; Revised version received 19 January 1990; Accepted 22 January 1990)
Key words: Conduction velocity; Motor nerve; Autonomic nerve; Streptozotocin diabetes We investigated the conduction velocity of motor and autonomic nerves, motor nerve to foot interosseous muscle and cervical vagus and sympathetic nerve, in streptozotocin diabetic rats (I-3 months duration of diabetes) and compared it with that of age-matched controls. In diabetic rats, the motor nerve conduction velocity was significantly reduced but the conduction velocity of cervical vagus and sympathetic nerves was not reduced.
It is well known that the motor and sensory nerve conduction velocity become slowed down in diabetes [2, 10, 15]. We studied the blood pressure and heart rate changes at rest and on tilt in streptozotocin diabetic rats and found postural hypotension, the autonomic neuropathy [8]. Therefore, we wondered whether conduction velocity of cervical sympathetic and vagus would occur, as well as reduced motor nerve conduction velocity. We examined the conduction velocity of motor nerve and cervical vagus and sympathetic nerve. We found a reduced motor nerve conduction velocity but no changes in cervical autonomic nerves. Male Wistar rats of 7 weeks old, weighing about 200 g, were purchased from a commercial source. The diabetic group was injected 60 mg/kg streptozotocin dissolved in citrate buffer (50 raM, pH 4.4) and the normal control group was only injected the vehicle, the citrate buffer. They were allowed free access to food and water [7, 11]. They were anesthetized with Nembutal 40 mg/kg. Tracheostomy was performed and then, left and right cervical vagus and sympathetic nerves were dissected out clearly for stimulation and recording. Initially, motor nerve conduction velocity was determined by stimulating the sciatic nerve at the sciatic notch and Achilles-tendon region and recording the evoked electromyogram of the lower limb interosseous muscle [18, 21], with needle electrodes for recording an electroencephaCorrespondence: S. Homma, Department of Physiology, Niigata University School of Medicine, Niigata 951, Japan. 0304-3940/90/$ 03.50 © 1990 Elsevier Scientific Publishers Ireland Ltd.
30 TABLE 1 DIABETIC DURATION, BODY WEIGHT AND BLOOD GLUCOSE OF RATS USED IN THIS EXPERIMENT Normal
DM
P
Days after STZ
(1-2M) (2-3M)
48.7 +_2.46 (n = 6) 87.0 +__2.20 (n = 6)
46.2+2.75 (n= 5) 84.8+_2.48 (n=5)
NS NS
Body weight
(1-2M) (2 3M)
473 + 22.2 573-+26.2
308 + 9.5 308 +_24.0
0.001 0.001
Blood glucose
(I-2M) (2-3M)
136 _+ 11.5 132+8.7
544 + 42.2 628 _+25.4
0.001 0.001
logram (NE-223S, Nikonkohden, Japan). The stimulus pulse was 0.1 ms and 1 V from a stimulator (SEN 2101, Nihonkohden, Japan). The electromyogram was recorded with a conventional biophysical amplifier and oscilloscope (AB-620G, time constant, 0.003 s and VC-10, Nihonkohden, Japan) and averaged 16 times with an averager (ATAC 201, Nihonkohden, Japan). The vagus was severed as centrally as possible and the peripheral end was kept intact. The sympathetic nerve was severed just preganglionic to the cervical sympathetic ganglion and the trunk to the heart was kept intact. The mineral oil pool was made around the neck. The cut end of the cervical nerve was lifted up in the oil with a bipolar stimulating electrode of silver-silver chlorided wire. The recording electrode was placed as caudally as possible. The evoked responses were also averaged 16 times. The nerves were stimulated with 0,1 ms pulses of 1-25 V. The temperature of the oil pool was kept at ground 32°C with a heating lamp. The body temperature was also kept at around 37°C with an autoregulated heater. Normal and diabetic rats were grouped as a 1-2 months group and a 2-3 months group after the streptozotocin or vehicle injection. Body weight and blood glucose level were listed in Table I. Numerical data were analyzed statistically using Student's t-test. As is shown in Table II, motor nerve conduction velocity was significantly reduced in 1-2 months and 2-3 months diabetic rats. For the determination of normal autonomic nerve conduction velocities (Figs. 1 and 2 and Tables IIIA and B), the threshold for evoking components of the cornTABLE II COMPARISON OF MOTOR NERVE CONDUCTION VELOCITY (m/s)
1-2 M 2-3 M
Normal
DM
P
45.6_+ 1.16 (6) 45.6_+ 1.51 (6)
39.9+_2.17(5) 40.9_+ 1.29 (5)
0.05 0.05
31 Fig. 2
Fig. 1
~OOuV lOmS--J
lOreS
'
Fig. 1. An example of averaged (16 times)-evokedcompound action potential of cervical vagus nerve of normal rat. Lower trace, 5 peaks by the stimulation of 0. I ms, 3 V. Upper trace shows the faster sweep of the first peak of the lower trace (indicated by e). Conduction velocity of 1st peak was 26.3 m/s (A), 2nd peak 2.5 m/s (delta-B), 3rd peak 1.25 m/s (CI), 4th peak 0.74 m/s (C3), 5th peak 0.45 m/s, C2 component lacking (see text). Calibrations are shown at right side. Fig. 2. Two examples of averaged (16 times)-evokedcompound action potentials of cervical sympathetic nerve of normal rats. Upper trace, 4 peaks by the stimulation of 0.1 ms, 4 V and lower trace, 3 peaks by the stimulation of 0.1 ms, 7 V. Upper trace, conduction velocity of 1st peak was 1.17 m/s (C1), 2nd peak 0.71 m/s (C2), 3rd peak 0.45 m/s (C3), 4th peak 0,29 m/s (C4). Lower trace, 1st peak 0.80 m/s (C2), 2nd peak 0.47 m/s (C3), 3rd peak 0.28 m/s (C4). C1 lacking (see text). Calibrations are shown at right side. pound action potentials o f the cervical autonomic nerve was evaluated. The threshold for the vagal first peak component was evoked by a stimulus o f 0.1 ms, 0.5-1 V, and the conduction velocity was 20.6+ 1.90 ( n = 14). The first peak in this study (A in Table IliA), probably includes the first (A) and second peak (delta) by N o s a k a et al., the conduction velocity was 28,3 _+8.8 and 16.44-4.0, respectively. I f we divide our first peak into two groups according to a conduction velocity o f 20 m/s, the mean of them was 25.44-1.45 ( n = 8 ) and 14,1 4- 1.84 (n=6), the former probably corresponding to the first peak and the latter to the second peak o f N o s a k a et al. [16]. The threshold for evoking other components (Fig. 1 and Table IIIA) for the vagus was 3-12 V. The second peak in this study was 2.0-3.5 m/s for conduction velocity and probably corresponds to delta-B [16]. Other components were 0 . 3 7 - 1 . 8 8 m/s for conduction velocity and they probably correspond to C [16]. Peaks o f the C group were arbitrarily divided into four, from the C1 to the C4 component in this study (Table IliA). The conduction velocity o f the cervical sympathetic nerve in this study was 0.28-1.68 m/s and classified into C 1 - C 4 according to their peak as in the vagus nerve (Fig. 2 and Table IIIB). The threshold for evoking all components was 0.1 ms and 1-13 V. The conduction velocity can be included in the C group of the vagus nerve [16]. As shown in Tables I l i A and B, there were no statistical differences in conduction velocities between the normal and diabetic cervical vagus and sympathetic trunk. It is well known that in diabetic animal models the m o t o r nerve conduction velocity slows down as well as in sensory nerves [2], such as the saphenous nerve [17], the tibial nerve [5], and the sural and tibial nerve [14]. A reduced conduction velocity
32 TABLE I l i a COMPARISON OF CONDUCTION VELOCITY OF CERVICAL VAGUS NERVE BETWEEN NORMAL (N) AND DIABETIC (DM) INCLUDING RATS OF 1-3 M DIABETIC DURATION, ALL STATISTICALLY INSIGNIFICANT A
B
C1
C2
C3
C4
N
20.65-1.90 (n = 14)
2.51+0.189 (n = 7)
1.47+0.071 (n = 13)
0.86+0.023 (n = 8)
0.68+0.012 (n = 14)
0.45+_0.012 (n = 14)
D M
21.05-2.07 (n= 12)
2.77_+0.151 (n =6)
1.48_+0.045 (n = 12)
0.95_+0,037 (n=9)
0.66+0.021 (n=9)
0.43+0,038 (n = 1t)
TABLE IIIB COMPARISON OF CONDUCTION VELOCITY OF CERVICAL SYMPATHETIC TRUNK (m/s) BETWEEN NORMAL (N) AND DIABETIC (DM), ALL STATISTICALLY INSIGNIFICANT C1
C2
C3
C4
I-2M
N (n=4) DM (n=3)
1.44+0.103 1.46+0.118
0.79+0.097 0.83+0.062
0.51 +0.033 0.51 5-0.013
0.33+0.017 0.30+0.022
2-3M
N (n=5) DM (n=5)
1.32+0.050 1.35-+0.062
0.87+0.049 0.77+0.039
0.555-0.035 0.51-+0.013
0.34-+0.017 0.31-+0.011
l 3M
N (n=9) DM (n= 8)
1.37+0.054 1.35 +0.062
0.845-0.049 0.77 _+0.039
0.535-0.024 0.51 +0.013
0.335-0.011 0.31 +0.011
was found in both sensory and motor nerve fibers of the sciatic nerve but no slowing in vagus nerve fibers of autonomic function [2]. The slowing was uniform along the axon from the roots to the distal tibial nerve [2]. In the saphenous nerve of streptozotocin diabetic rats, the fastest A-alpha fibers were affected most and slowed down in conduction velocity, followed by the myelinated A-delta fibers but C-fibers were not significantly affected [6]. We also confirmed the slowing of motor nerve conduction velocity, but could not find the slowing of conduction velocity in C-fibers of the cervical vagus and sympathetic nerve, neither in myelinated fibers of the cervical vagus. Myelinated fibers are present in the cervical vagus trunk. However, slowing of them was not detected in this study. We do not exclude the possibility of slowing of the more peripheral autonomic nerves near or within the effectors. Julu [6] discussed the contribution of non-enzymatic glycosylation of the major structural myelin protein [20] and that this could add positive charges on the molecules [I], leading to the increase of the capacitance of myelin and slowing down of the conduction velocity. He also discussed the contribution of an altered lipid composition of myelin, deriving from metabolic disorders of essential fatty acids [3]. The mechanisms of diabetic neuropathy and functional impairment, including reduced conduction velocity, are listed as follows: (i) changes of endoneurial vessels, leading to anoxia and infarcts [12], (ii) metabolic disorders of reduced free myoi-
33
nositol, or reduced Na +/K +-ATPase activity [4], reduced amino acid uptake [19] and protein synthesis [12], (iii) protein changes of nonenzymatic glycosylation [9], and (iv) impairment of axonal transport, especially slow axonal transport [13]. 1 Bunn, H.F., Nonenzymatic glycosylation of protein: relevance to diabetes, Am. J. Meal., 70 (1981) 325330. 2 Eliasson, S.G., Nerve conduction changes in experimental diabetes, J. Clin. Invest., 43 (1954) 23532358. 3 Faas, F.H. and Carter, W.J., Altered fatty acid desaturation and microsomal fatty acid composition in the streptozotocin diabetic rat, Lipids, 15 (1980) 953-961. 4 Greene, D.A. and Lattimer, S.A., Impaired rat sciatic nerve sodium-potassium ATPase in acute streptozotocin diabetes and its correction by dietary myo-inositol supplementation, J. Clin. Invest., 72 (1983) 1058-1062. 5 Hildebrand, J., Joftroy, A., Graft, G. and CoOrs, C., Neuromuscular changes with alloxan hyperglycemia, Arch. Neurol., 18 (1968) 633-641. 6 Julu, P.O.O., The correlation between sensory nerve conduction velocities and three metabolic indices in rats treated with streptozotocin, Diabetologla, 31 (1988) 247-253. 7 Karakida, T., Ito, S. and Homma, S., In vitro motor activity of intestinal segments of streptozotocin diabetic rats, J. Auto n. Nerv. Syst., 26 (1989) 43-50. 8 Karakida, T., Yamazaki, Y. and Homma, S., Blood pressure and heart rate changes in streptozotocin diabetic rats, Jpn. J. Physiol., 39 (Suppl.) (1989) s104. 9 Kennedy, L. and Baynes, J.W., Non-enzymatic glycosylation and the chronic complications of diabetes: an overview, Diabetologla, 26 (I 984) 93-98. 10 Liberson, W.T., Determination of conduction velocities in the sensory nerve fibers, Electroenceph. Clin. Neurophysiol., 13 (1961) 319. 11 Liu, H.-S., Karakida, T. and Homma, S., Acetylcholine and substance P responses of intestinal smooth muscles in streptozotocin diabetic diabetic rats, Jpn. J. Physiol., 38 (1988) 787-797. 12 Low, P.A., Recent advances in the pathogenesis of diabetic neuropathy, Muscle Nerv., 10 (1987) 121128. 13 Medori, R., Jenich, H., Autillio-Gambetti and Gambetti, P., Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models, J. Neurosci., 8 (1988) 1814-1821. 14 Moore, S.A., Peterson, R., Felten, D.L. and O'Connor, B.L., A quantitative comparison of motor and sensory conduction velocities in short- and long-term streptozotocin- and alloxan-diabetic rats, J. Neurol. Sci., 48 (1980) 133-152. 15 Mudler, D.W., Lambert, E.H., Bastron, J.A. and Sprague, R.G., The neuropathies associated with diabetes meUitus, Neurology (Minneap.), 11 (1961) 275-284. 16 Nosaka, S., Yasunaga, K. and Kawano, M., Vagus cardioinhibitory fibers in rats, Pfliig. Arch. Eur. J. Physiol., 379 (1979) 281-285. 17 Preston, G.M., Peripheral neuropathy in alloxan-diabetic rat, J. Physiol. (Lond.), 189 (1967) 49-50P (Abstract). 18 Sharma, A.K. and Thomas, P.K., Peripheral nerve structure and function in experimental diabetes, J. Neurol. Sci., 23 (1975) 1-15. 19 Thomas, P.K., Wright D.W. and Tzebelikos, E., Amino acid uptake by dorsal root ganglia from streptozotocin-diabetic rats, J. Neurol. Neurosurg. Psychiatry, 47 (1984) 912-916. 20 Vlassara, H., Brownlee, M. and Cerami, A., Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats, Diabetes, 32 (1983) 670-674. 21 Whiteley, S.J. and Tomlinson, D.R., Motor nerve conduction velocity and nerve polyols in mice with short-term genetic or streptozotocin-induced diabetes, Exp. Neurol., 89 (1985) 314-321.
29
Elsevier Scientific Publishers Ireland Ltd.
N S L 06853
Conduction velocity of motor nerve and cervical sympathetic and vagus nerve in streptozotocin diabetic rats Y u k o Yamazaki, T a k e o Karakida and Shinji H o m m a Department of Physiology, Niigata UniversitySchoolof Medicine, Niigata (Japan) (Received I l December 1989; Revised version received 19 January 1990; Accepted 22 January 1990)
Key words: Conduction velocity; Motor nerve; Autonomic nerve; Streptozotocin diabetes We investigated the conduction velocity of motor and autonomic nerves, motor nerve to foot interosseous muscle and cervical vagus and sympathetic nerve, in streptozotocin diabetic rats (I-3 months duration of diabetes) and compared it with that of age-matched controls. In diabetic rats, the motor nerve conduction velocity was significantly reduced but the conduction velocity of cervical vagus and sympathetic nerves was not reduced.
It is well known that the motor and sensory nerve conduction velocity become slowed down in diabetes [2, 10, 15]. We studied the blood pressure and heart rate changes at rest and on tilt in streptozotocin diabetic rats and found postural hypotension, the autonomic neuropathy [8]. Therefore, we wondered whether conduction velocity of cervical sympathetic and vagus would occur, as well as reduced motor nerve conduction velocity. We examined the conduction velocity of motor nerve and cervical vagus and sympathetic nerve. We found a reduced motor nerve conduction velocity but no changes in cervical autonomic nerves. Male Wistar rats of 7 weeks old, weighing about 200 g, were purchased from a commercial source. The diabetic group was injected 60 mg/kg streptozotocin dissolved in citrate buffer (50 raM, pH 4.4) and the normal control group was only injected the vehicle, the citrate buffer. They were allowed free access to food and water [7, 11]. They were anesthetized with Nembutal 40 mg/kg. Tracheostomy was performed and then, left and right cervical vagus and sympathetic nerves were dissected out clearly for stimulation and recording. Initially, motor nerve conduction velocity was determined by stimulating the sciatic nerve at the sciatic notch and Achilles-tendon region and recording the evoked electromyogram of the lower limb interosseous muscle [18, 21], with needle electrodes for recording an electroencephaCorrespondence: S. Homma, Department of Physiology, Niigata University School of Medicine, Niigata 951, Japan. 0304-3940/90/$ 03.50 © 1990 Elsevier Scientific Publishers Ireland Ltd.
30 TABLE 1 DIABETIC DURATION, BODY WEIGHT AND BLOOD GLUCOSE OF RATS USED IN THIS EXPERIMENT Normal
DM
P
Days after STZ
(1-2M) (2-3M)
48.7 +_2.46 (n = 6) 87.0 +__2.20 (n = 6)
46.2+2.75 (n= 5) 84.8+_2.48 (n=5)
NS NS
Body weight
(1-2M) (2 3M)
473 + 22.2 573-+26.2
308 + 9.5 308 +_24.0
0.001 0.001
Blood glucose
(I-2M) (2-3M)
136 _+ 11.5 132+8.7
544 + 42.2 628 _+25.4
0.001 0.001
logram (NE-223S, Nikonkohden, Japan). The stimulus pulse was 0.1 ms and 1 V from a stimulator (SEN 2101, Nihonkohden, Japan). The electromyogram was recorded with a conventional biophysical amplifier and oscilloscope (AB-620G, time constant, 0.003 s and VC-10, Nihonkohden, Japan) and averaged 16 times with an averager (ATAC 201, Nihonkohden, Japan). The vagus was severed as centrally as possible and the peripheral end was kept intact. The sympathetic nerve was severed just preganglionic to the cervical sympathetic ganglion and the trunk to the heart was kept intact. The mineral oil pool was made around the neck. The cut end of the cervical nerve was lifted up in the oil with a bipolar stimulating electrode of silver-silver chlorided wire. The recording electrode was placed as caudally as possible. The evoked responses were also averaged 16 times. The nerves were stimulated with 0,1 ms pulses of 1-25 V. The temperature of the oil pool was kept at ground 32°C with a heating lamp. The body temperature was also kept at around 37°C with an autoregulated heater. Normal and diabetic rats were grouped as a 1-2 months group and a 2-3 months group after the streptozotocin or vehicle injection. Body weight and blood glucose level were listed in Table I. Numerical data were analyzed statistically using Student's t-test. As is shown in Table II, motor nerve conduction velocity was significantly reduced in 1-2 months and 2-3 months diabetic rats. For the determination of normal autonomic nerve conduction velocities (Figs. 1 and 2 and Tables IIIA and B), the threshold for evoking components of the cornTABLE II COMPARISON OF MOTOR NERVE CONDUCTION VELOCITY (m/s)
1-2 M 2-3 M
Normal
DM
P
45.6_+ 1.16 (6) 45.6_+ 1.51 (6)
39.9+_2.17(5) 40.9_+ 1.29 (5)
0.05 0.05
31 Fig. 2
Fig. 1
~OOuV lOmS--J
lOreS
'
Fig. 1. An example of averaged (16 times)-evokedcompound action potential of cervical vagus nerve of normal rat. Lower trace, 5 peaks by the stimulation of 0. I ms, 3 V. Upper trace shows the faster sweep of the first peak of the lower trace (indicated by e). Conduction velocity of 1st peak was 26.3 m/s (A), 2nd peak 2.5 m/s (delta-B), 3rd peak 1.25 m/s (CI), 4th peak 0.74 m/s (C3), 5th peak 0.45 m/s, C2 component lacking (see text). Calibrations are shown at right side. Fig. 2. Two examples of averaged (16 times)-evokedcompound action potentials of cervical sympathetic nerve of normal rats. Upper trace, 4 peaks by the stimulation of 0.1 ms, 4 V and lower trace, 3 peaks by the stimulation of 0.1 ms, 7 V. Upper trace, conduction velocity of 1st peak was 1.17 m/s (C1), 2nd peak 0.71 m/s (C2), 3rd peak 0.45 m/s (C3), 4th peak 0,29 m/s (C4). Lower trace, 1st peak 0.80 m/s (C2), 2nd peak 0.47 m/s (C3), 3rd peak 0.28 m/s (C4). C1 lacking (see text). Calibrations are shown at right side. pound action potentials o f the cervical autonomic nerve was evaluated. The threshold for the vagal first peak component was evoked by a stimulus o f 0.1 ms, 0.5-1 V, and the conduction velocity was 20.6+ 1.90 ( n = 14). The first peak in this study (A in Table IliA), probably includes the first (A) and second peak (delta) by N o s a k a et al., the conduction velocity was 28,3 _+8.8 and 16.44-4.0, respectively. I f we divide our first peak into two groups according to a conduction velocity o f 20 m/s, the mean of them was 25.44-1.45 ( n = 8 ) and 14,1 4- 1.84 (n=6), the former probably corresponding to the first peak and the latter to the second peak o f N o s a k a et al. [16]. The threshold for evoking other components (Fig. 1 and Table IIIA) for the vagus was 3-12 V. The second peak in this study was 2.0-3.5 m/s for conduction velocity and probably corresponds to delta-B [16]. Other components were 0 . 3 7 - 1 . 8 8 m/s for conduction velocity and they probably correspond to C [16]. Peaks o f the C group were arbitrarily divided into four, from the C1 to the C4 component in this study (Table IliA). The conduction velocity o f the cervical sympathetic nerve in this study was 0.28-1.68 m/s and classified into C 1 - C 4 according to their peak as in the vagus nerve (Fig. 2 and Table IIIB). The threshold for evoking all components was 0.1 ms and 1-13 V. The conduction velocity can be included in the C group of the vagus nerve [16]. As shown in Tables I l i A and B, there were no statistical differences in conduction velocities between the normal and diabetic cervical vagus and sympathetic trunk. It is well known that in diabetic animal models the m o t o r nerve conduction velocity slows down as well as in sensory nerves [2], such as the saphenous nerve [17], the tibial nerve [5], and the sural and tibial nerve [14]. A reduced conduction velocity
32 TABLE I l i a COMPARISON OF CONDUCTION VELOCITY OF CERVICAL VAGUS NERVE BETWEEN NORMAL (N) AND DIABETIC (DM) INCLUDING RATS OF 1-3 M DIABETIC DURATION, ALL STATISTICALLY INSIGNIFICANT A
B
C1
C2
C3
C4
N
20.65-1.90 (n = 14)
2.51+0.189 (n = 7)
1.47+0.071 (n = 13)
0.86+0.023 (n = 8)
0.68+0.012 (n = 14)
0.45+_0.012 (n = 14)
D M
21.05-2.07 (n= 12)
2.77_+0.151 (n =6)
1.48_+0.045 (n = 12)
0.95_+0,037 (n=9)
0.66+0.021 (n=9)
0.43+0,038 (n = 1t)
TABLE IIIB COMPARISON OF CONDUCTION VELOCITY OF CERVICAL SYMPATHETIC TRUNK (m/s) BETWEEN NORMAL (N) AND DIABETIC (DM), ALL STATISTICALLY INSIGNIFICANT C1
C2
C3
C4
I-2M
N (n=4) DM (n=3)
1.44+0.103 1.46+0.118
0.79+0.097 0.83+0.062
0.51 +0.033 0.51 5-0.013
0.33+0.017 0.30+0.022
2-3M
N (n=5) DM (n=5)
1.32+0.050 1.35-+0.062
0.87+0.049 0.77+0.039
0.555-0.035 0.51-+0.013
0.34-+0.017 0.31-+0.011
l 3M
N (n=9) DM (n= 8)
1.37+0.054 1.35 +0.062
0.845-0.049 0.77 _+0.039
0.535-0.024 0.51 +0.013
0.335-0.011 0.31 +0.011
was found in both sensory and motor nerve fibers of the sciatic nerve but no slowing in vagus nerve fibers of autonomic function [2]. The slowing was uniform along the axon from the roots to the distal tibial nerve [2]. In the saphenous nerve of streptozotocin diabetic rats, the fastest A-alpha fibers were affected most and slowed down in conduction velocity, followed by the myelinated A-delta fibers but C-fibers were not significantly affected [6]. We also confirmed the slowing of motor nerve conduction velocity, but could not find the slowing of conduction velocity in C-fibers of the cervical vagus and sympathetic nerve, neither in myelinated fibers of the cervical vagus. Myelinated fibers are present in the cervical vagus trunk. However, slowing of them was not detected in this study. We do not exclude the possibility of slowing of the more peripheral autonomic nerves near or within the effectors. Julu [6] discussed the contribution of non-enzymatic glycosylation of the major structural myelin protein [20] and that this could add positive charges on the molecules [I], leading to the increase of the capacitance of myelin and slowing down of the conduction velocity. He also discussed the contribution of an altered lipid composition of myelin, deriving from metabolic disorders of essential fatty acids [3]. The mechanisms of diabetic neuropathy and functional impairment, including reduced conduction velocity, are listed as follows: (i) changes of endoneurial vessels, leading to anoxia and infarcts [12], (ii) metabolic disorders of reduced free myoi-
33
nositol, or reduced Na +/K +-ATPase activity [4], reduced amino acid uptake [19] and protein synthesis [12], (iii) protein changes of nonenzymatic glycosylation [9], and (iv) impairment of axonal transport, especially slow axonal transport [13]. 1 Bunn, H.F., Nonenzymatic glycosylation of protein: relevance to diabetes, Am. J. Meal., 70 (1981) 325330. 2 Eliasson, S.G., Nerve conduction changes in experimental diabetes, J. Clin. Invest., 43 (1954) 23532358. 3 Faas, F.H. and Carter, W.J., Altered fatty acid desaturation and microsomal fatty acid composition in the streptozotocin diabetic rat, Lipids, 15 (1980) 953-961. 4 Greene, D.A. and Lattimer, S.A., Impaired rat sciatic nerve sodium-potassium ATPase in acute streptozotocin diabetes and its correction by dietary myo-inositol supplementation, J. Clin. Invest., 72 (1983) 1058-1062. 5 Hildebrand, J., Joftroy, A., Graft, G. and CoOrs, C., Neuromuscular changes with alloxan hyperglycemia, Arch. Neurol., 18 (1968) 633-641. 6 Julu, P.O.O., The correlation between sensory nerve conduction velocities and three metabolic indices in rats treated with streptozotocin, Diabetologla, 31 (1988) 247-253. 7 Karakida, T., Ito, S. and Homma, S., In vitro motor activity of intestinal segments of streptozotocin diabetic rats, J. Auto n. Nerv. Syst., 26 (1989) 43-50. 8 Karakida, T., Yamazaki, Y. and Homma, S., Blood pressure and heart rate changes in streptozotocin diabetic rats, Jpn. J. Physiol., 39 (Suppl.) (1989) s104. 9 Kennedy, L. and Baynes, J.W., Non-enzymatic glycosylation and the chronic complications of diabetes: an overview, Diabetologla, 26 (I 984) 93-98. 10 Liberson, W.T., Determination of conduction velocities in the sensory nerve fibers, Electroenceph. Clin. Neurophysiol., 13 (1961) 319. 11 Liu, H.-S., Karakida, T. and Homma, S., Acetylcholine and substance P responses of intestinal smooth muscles in streptozotocin diabetic diabetic rats, Jpn. J. Physiol., 38 (1988) 787-797. 12 Low, P.A., Recent advances in the pathogenesis of diabetic neuropathy, Muscle Nerv., 10 (1987) 121128. 13 Medori, R., Jenich, H., Autillio-Gambetti and Gambetti, P., Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models, J. Neurosci., 8 (1988) 1814-1821. 14 Moore, S.A., Peterson, R., Felten, D.L. and O'Connor, B.L., A quantitative comparison of motor and sensory conduction velocities in short- and long-term streptozotocin- and alloxan-diabetic rats, J. Neurol. Sci., 48 (1980) 133-152. 15 Mudler, D.W., Lambert, E.H., Bastron, J.A. and Sprague, R.G., The neuropathies associated with diabetes meUitus, Neurology (Minneap.), 11 (1961) 275-284. 16 Nosaka, S., Yasunaga, K. and Kawano, M., Vagus cardioinhibitory fibers in rats, Pfliig. Arch. Eur. J. Physiol., 379 (1979) 281-285. 17 Preston, G.M., Peripheral neuropathy in alloxan-diabetic rat, J. Physiol. (Lond.), 189 (1967) 49-50P (Abstract). 18 Sharma, A.K. and Thomas, P.K., Peripheral nerve structure and function in experimental diabetes, J. Neurol. Sci., 23 (1975) 1-15. 19 Thomas, P.K., Wright D.W. and Tzebelikos, E., Amino acid uptake by dorsal root ganglia from streptozotocin-diabetic rats, J. Neurol. Neurosurg. Psychiatry, 47 (1984) 912-916. 20 Vlassara, H., Brownlee, M. and Cerami, A., Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats, Diabetes, 32 (1983) 670-674. 21 Whiteley, S.J. and Tomlinson, D.R., Motor nerve conduction velocity and nerve polyols in mice with short-term genetic or streptozotocin-induced diabetes, Exp. Neurol., 89 (1985) 314-321.
