Neuritin mediates nerve growth factor-induced axonal regeneration and is deficient in experimental diabetic neuropathy.

Objective: Axonal regeneration is defective in both experimental and clinical diabetic neuropathy, contributing to loss of axonal extremities and neuronal dysfunction. The mechanisms behind this failure are not fully understood; however, a deficit in neurotrophic support and signaling has been implicated.

Research Design And Methods: We investigated the expression of neuritin (also known as candidate plasticity gene 15, cpg15) in the sensory nervous system of control rats and rats with streptozotocin (STZ)-induced diabetes using microarray PCR, Western blotting, and immunocytochemical analysis.

Altered expression of iron transport proteins in streptozotocin-induced diabetic rat kidney.

Diabetes mellitus is associated with altered iron homeostasis in both human and animal diabetic models. Iron is a metal oxidant capable of generating reactive oxygen species (ROS) and has been postulated to contribute to diabetic nephropathy. Two proteins involved in iron metabolism that are expressed in the kidney are the divalent metal transporter, DMT1 (Slc11a2), and the Transferrin Receptor (TfR).

Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of rats with experimental diabetes.

In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation which resembles axotomy. This raises the question: does inappropriate establishment of an axotomised neuronal phenotype contribute to diabetic neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse-transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the array for expression of (a) genes that are upregulated by axotomy, (b) proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic rats compared to controls; thus, no axotomised phenotype was established.