Peripheral, but not Central, Nervous System Abnormalities are Reversed by Pancreatic Islet Transplantation in Diabetic Lewis Rats

Abstract

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.

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

“…This latter interpretation would be in line with our observation that NAA ratios in the brain of STZ-diabetic rats were reduced well before functional and structural abnormalities are known to occur in this model. Deficits in learning and memory and in signal transduction, for example, become detectable at 2 to 3 months after diabetes induction and develop gradually thereafter [9,6,7]. Whether reductions in NAA, as an early marker of neuronal dysfunction in STZ-diabetes, are causally related to the behavioural, neurophysiological and structural cerebral changes that occur later on is not known.…”

“…tory and visual evoked potentials [6,7] and morphological alterations [8]. The development of these deficits is related to diabetes duration and the severity of hyperglycaemia [6].…”

Early, but Not Advanced, Glomerulopathy Is Reversed by Pancreatic Islet Transplants in Experimental Diabetic Rats: Correlation With Glomerular Extracellular Matrix mRNA Levels

“…Three diabetic rats transplanted at 8 months of diabetes duration died during or immediately after surgery for transplantation and were substituted with other animals. The day before killing, one TDa and one TDc rat (as well as one 12-month D rat) died under anesthesia during neuroelectrophysiological measurements, performed in parallel with the assessment of renal function and structure and reported elsewhere (17). Induction of diabetes.…”

Nerve conduction velocity and evoked potential latencies in streptozotocin‐diabetic rats: effects of treatment with an angiotensin converting enzyme inhibitor

“…After two to three months of experimental diabetes, structural changes develop that may be more difficult to reverse [35,12,36]. Still, studies with insulin treatment, through subcutaneous implants or islet cell grafts, show that deficits in nerve conduction velocity are potentially reversible up to six months after diabetes induction [12,37]. In the latter studies, treatment led to a complete reversal of the diabetic state.…”

“…The potential reversibility of increased evoked potential latencies in experimental diabetes has thus far been addressed in a limited number of studies. In one study, pancreatic islet transplantation, performed at a diabetes duration of four months, did not improve BAEP, VEP and somatosensory evoked potential latencies at eight months of diabetes [37]. In another study, insulin treatment through subcutaneous implants, initiated after six months of diabetes, led to a partial restoration of both BAEP and VEP latencies [12].…”