Yuichi Murakawa

Diabetic neuropathy – a continuing enigma

In this article we will review the clinical signs and symptoms of diabetic somatic polyneuropathy (DPN), its prevalence and clinical management. Staging and classification of DPN will be exemplified by various staging paradigms of varied sophistication. The results of therapeutic clinical trials will be summarized. The pathogenesis of diabetic neuropathy reviews an extremely complex issue that is still not fully understood. Various recent advances in the understanding of the disease will be discussed, particularly with respect to the differences between neuropathy in the two major types of diabetes. The neuropathology and natural history of diabetic neuropathy will be discussed pointing out the heterogeneities of the disease. Finally, the various prospective therapeutic avenues will be dealt with and discussed. Copyright

Impaired glucose tolerance and insulinopenia in the GK‐rat causes peripheral neuropathy

Recent studies indicate that impaired glucose tolerance (IGT) in man is a causative factor in idiopathic sensory neuropathy, and that insulinopenia may contribute substantially to the severity of diabetic peripheral neuropathy. The effect of sustained IGT and progressive insulinopenia in the absence of overt hyperglycemia on peripheral nerve abnormalities was examined in the Goto–Kakizaki (GK)‐rat.

Expression and localization of insulin receptor in rat dorsal root ganglion and spinal cord

Abstract  The expression and localization of the insulin receptor (IR) was examined in rat dorsal root ganglia (DRG) and spinal cord using Western blotting, in situ hybridization and immunocytochemistry. Western blotting showed that the molecular weight of the IR β subunit was higher in PNS than that found in CNS. Both IR mRNA and protein expressions were highest in small‐sized sensory DRG neurons and myelinated sensory root fibers expressed higher levels of IR protein than myelinated anterior root fibers. In the spinal cord, IR immunoreactive neurons were present in lateral lamina V and in lamina X, suggesting the presence of IR in nociceptive pathways. Electronmicroscopy of DRGs revealed a polarized localization of the IR in abaxonal Schwann cell membranes, outer mesaxons in close vicinity to tight junctions of both myelinating and non‐myelinating Schwann cells and to plasma membranes of sensory neurons. From these findings, we speculate that insulin may play a role in sensory fibers involved in nociceptive function often perturbed in diabetic neuropathy. The high expression of IR localizing to tight junctions of dorsal root mesaxons of DRGs may suggest a regulatory role on barrier functions compensating for the lack of a blood–nerve barrier in dorsal root ganglia. This is consistent with the colocalization of IR with tight junctions of the paranodal barrier and endoneurial endothelial cells in peripheral nerve.

Insulin receptor in rat peripheral nerve: its localization and alternatively spliced isoforms

Diabetic neuropathy accompanies both Type 1 and Type 2 diabetes, although it shows in both humans and animal models distinct differences between the two types of diabetes. Progressive paranodal degenerations occurring in Type 1, but not in Type 2, diabetes is believed to account for the more severe functional deficits in Type 1 diabetic rats. This suggests that factors other than hyperglycemia, such as insulin deficiency, may play a pathogenetic role. In this study, we investigated the immunolocalization of the insulin receptor (IR) and the expression of its two alternatively spliced isoforms in adult rat peripheral nerve.

Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes

Neuropathic pain is common in diabetic patients. Degeneration of sensory C‐fibers in peripheral nerve plays a prominent role in the generation of neuropathic pain. We examined degenerative changes of C‐fibers in two rat models with type 1 and type 2 diabetes.