Effect of islet transplantation on neuroelectrophysiological abnormalities in diabetic inbred Lewis rats: comparison of primary versus secondary prevention.

BACKGROUND: Neuroelectrophysiological abnormalities in diabetes indicate nervous function failure. Restoration of euglycemia by islet transplantation may prevent or reverse these abnormalities. METHODS: Pancreatic islets were transplanted in inbred Lewis rats after 15 days (Ta12, primary prevention) or 8 months (Tb12, secondary prevention) from streptozotocin-induced diabetes. Transplanted and control (normal and diabetic) rats were followed for a total period of 12 months. Metabolic parameters, somato-sensory, brain-stem auditory, and visual evoked potentials were determined at the beginning and at the end of the study and before transplantation for secondary prevention. RESULTS: The metabolic parameters in transplanted animals were similar to those of normal animals. Ta12 and normal group somato-sensory conduction velocities did not vary and were always significantly higher than those of diabetic animals. By contrast, Tb12 group conduction velocities showed only a partial improvement, values lying between those of diabetic and normal rats. Brain-stem auditory (waves I, II, and III) latencies in Ta12 group were similar to those of normal rats and significantly lower than those of diabetic animals (wave I: P<0.01; waves II and III: P<0.05). Tb12 group wave I and II latency values remained altered (P<0.005 and P<0.01 versus normal values respectively). Visual evoked potentials-P1 wave latencies in transplanted rats were always higher than those of normal and diabetic animals. CONCLUSIONS: After primary prevention, central and peripheral neurological alterations were abolished. After secondary prevention, transplantation beneficial effects were partial, occurring mainly at peripheral level. These results highlight the importance of early transplantation to prevent hyperglycemia-dependent neuroelectrophysiological alterations.

Autonomic involvement in multiple sclerosis: a pupillometric study.

To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.

Peripheral, but not central, nervous system abnormalities are reversed by pancreatic islet transplantation in diabetic Lewis rats.

Neuroelectrophysiological recordings represent a non-invasive and reproducible method of detecting central and peripheral nervous system alterations in diabetes mellitus. In order to evaluate whether the normalization of metabolic control obtained by pancreatic islet transplantation could reverse diabetic neuroelectrophysiological alterations, or prevent further deterioration, we used an experimental model in which pancreatic islets (n = 1200) were injected into the portal vein of inbred Lewis rats (used as islet donors as well as recipients). Islets were injected 4 months after diabetes induction, since previous work had shown functional but not morphological damage at the nervous tissue level at this stage of the disease. Visual (V), brainstem auditory (BA) and somatosensory (S) evoked potentials (EPs) were measured in streptozotocin-induced, islet-recipient diabetic rats (n = 7), streptozotocin-induced diabetic rats (n = 16) and non-diabetic control rats (n = 12). Metabolic parameters and electrophysiological recordings were evaluated before diabetes induction, before transplantation and 4 months later. After transplantation, glycaemic levels returned to normal values within 1 week and remained so until the end of the study, as confirmed by a normal oral glucose tolerance test and by an increase in body weight. Electrophysiological recordings were altered in diabetic animals before transplantation. Four months after transplantation EP recordings improved, with a detectable gradient from the peripheral to the central structures. SEPs were significantly improved in the peripheral tarsus-L6 tract and the L6-cortex tract (P < 0.005 and P < 0.01 versus diabetic rats) and were ameliorated without achieving statistical significance in the central L6-cortex tract. BAEP latency values tended to improve in transplanted rats, but the differences versus non-transplanted diabetic animals failed to reach significance. VEP values remained clearly pathological and even deteriorated after transplantation. These results show that normalization of metabolic control by pancreatic islet transplantation can reverse some of the already established neuroelectrophysiological alterations at the peripheral nervous system level, but does not affect other alterations at the central nervous system level.

Role of advanced glycation end-products (AGE) in late diabetic complications.

To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.