Neurochemical characterization of insulin receptor‐expressing primary sensory neurons in wild‐type and vanilloid type 1 transient receptor potential receptor knockout mice

Abstract

The insulin receptor (IR) is expressed by a subpopulation of primary sensory neurons (PSN), including a proportion of cells expressing the nociceptive transducer vanilloid type 1 transient receptor potential receptor (TRPV1). Recent data suggest functional links between the IR and other receptors, including TRPV1, which could be involved in the development of PSN malfunctions in pathological insulin secretion. Here we used combined immunohistochemical labelling on sections from L4-5 dorsal root ganglia of wild-type (WT) and TRPV1 knockout (KO) mice to examine the neurochemical properties of IR-expressing PSN and the possible effect of deletion of TRPV1 on those characteristics. We found that antibodies raised against the high-molecular-weight neurofilament (NF-200) and the neurofilament protein peripherin distinguished between small and large neurons. We also found that the IR was expressed predominantly by the small peripherin-immunopositive cells both in the WT and in the KO animals. IR expression, however, did not show any preference between the major subpopulations of the small cells, the calcitonin gene-related peptide (CGRP)-expressing and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons, either in the WT or in the KO mice. Nevertheless, a significant proportion of the IR-expressing cells also expressed TRPV1. Comparison of the staining pattern of these markers showed no difference between WT and KO animals. These findings indicate that the majority of the IR-expressing PSN are small neurons, which are considered as nociceptive cells. Furthermore, these data show that deletion of the TRPV1 gene does not induce any additional changes in neurochemical phenotype of nociceptive PSN.

Differentiation and migration of neural crest stem cells are stimulated by pancreatic islets

“…Insulin itself also acts as a trophic factor in neural crest development [13] after injury [14], and a subtype of sensory neurons expresses the insulin receptor [15]. Islet-mediated stimulation of NCSC differentiation in the cocultures may in turn promote NCSC production of additional growth-supporting factors, for example, TNF-a, IL-1, nerve growth factor, and leukemia inhibitory factor, which can be produced by peripheral glia or neurons [16,17].…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Of note, in a different study, BCTC was proposed to keep mice lean by inhibiting TRPV4 channels . TRPV1-positive sensory neurons possess high-affinity insulin receptors (Baiou et al, 2007). Insulin was suggested to facilitate the redistribution of TRPV1 from intracellular organelles to the plasma membrane and thereby sensitize the neurons to TRPV1 agonists (see Bishnoi and Premkumar, 2013).…”

A Role for Insulin in Diabetic Neuropathy

“…indicated that approximately 40% of DRG neurons express the insulin receptor and that approximately 75% of insulin receptor expressing neurons were co-labeled with peripherin (Baiou et al, 2007). TRPV1 co-labeling indicated 25% of all DRG neurons coexpress TRPV1 and the insulin receptor and that approximately 68% of TRPV1 positive neurons express the insulin receptor (Baiou et al, 2007). Furthermore, insulin receptor expression was not confined to one c-fiber subtype, as insulin receptor expressing neurons were co-labeled with either CGRP (peptidergic) or IB4 (non-peptidergic).…”