Péter Sántha

Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes

The system that regulates insulin secretion from β‐cells in the islet of Langerhans has a capsaicin‐sensitive inhibitory component. As calcitonin gene‐related peptide (CGRP)‐expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP‐containing primary sensory neurons is sensitive to capsaicin, the islet‐innervating sensory fibers may represent the capsaicin‐sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid typeu20031 transient receptor potential receptor (TRPV1) in CGRP‐expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin‐sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human typeu20032 diabetes mellitus. We found that CGRP‐expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non‐fasting, and mean 24‐h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP‐ and TRPV1‐coexpressing islet‐innervating fibers. These data indicate that CGRP‐containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet‐innervating capsaicin‐sensitive fibers may have a role in the development of reduced insulin secretion in human typeu20032 diabetes mellitus.

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

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. J. Comp. Neurol. 503:334–347, 2007.

Axotomy prevents capsaicin-induced sensory ganglion cell degeneration

A particular group of mammalian primary afferent neurons involved in nociception is characterized by its specific sensitivity to capsaicin, the pungent principle of red pepper. A striking manifestation of neuronal capsaicin sensitivity is the degeneration of a morphologically well characterized population of sensory ganglion cells following a systemic injection of this compound. The present study demonstrated that prior transection of the peripheral axons of these neurons protects them from the neurotoxic action of systemically administered capsaicin. It is suggested that this phenomenon is related to an impairment of axon transport mechanisms. It is concluded that maintenance of capsaicin sensitivity is critically dependent on the integrity of the peripheral branch of the primary sensory neuron and peripherally derived trophic factor(s) may profoundly influence the functional traits of sensory ganglion cells.

The foundation of sensory pharmacology: Nicholas (Miklós) Jancsó and the Szeged contribution

Capsaicin became an indispensable tool in pain research after the discovery of its unique pharmacological actions by Nicholas (Miklós) Jancsó Jr. in the late 1940s. This “History Article” introduces his achievements leading to the foundation of “sensory pharmacology” and subsequent research in that field at the University of Szeged, Hungary.

Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor

Apart from its pivotal role in the regulation of carbohydrate metabolism, insulin exerts important neurotrophic and neuromodulator effects on dorsal root ganglion (DRG) neurons. The neurite outgrowth-promoting effect is one of the salient features of insulin’s action on cultured DRG neurons. Although it has been established that a significant population of DRG neurons express the insulin receptor (InsR), the significance of InsR expression and the chemical phenotype of DRG neurons in relation to the neurite outgrowth-promoting effect of insulin has not been studied. Therefore, in this study by using immunohistochemical and quantitative stereological methods we evaluated the effect of insulin on neurite outgrowth of DRG neurons of different chemical phenotypes which express or lack the InsR. Insulin, at a concentration of 10 nM, significantly increased total neurite length, the length of the longest neurite and the number of branch points of cultured DRG neurons as compared to neurons cultured in control medium or in the presence of 1 μM insulin. In both the control and the insulin exposed cultures, ∼43% of neurons displayed InsR-immunoreactivity. The proportions of transient receptor potential vanilloid type 1 receptor (TRPV1)-immunoreactive (IR), calcitonin gene-related peptide (CGRP)-IR and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons amounted to ∼61%, ∼57%, and ∼31% of DRG neurons IR for the InsR. Of the IB4-positive population only neurons expressing the InsR were responsive to insulin. In contrast, TRPV1-IR nociceptive and CGRP-IR peptidergic neurons showed increased tendency for neurite outgrowth which was further enhanced by insulin. However, the responsiveness of DRG neurons expressing the InsR was superior to populations of DRG neurons which lack this receptor. The findings also revealed that besides the expression of the InsR, inherent properties of peptidergic, but not non-peptidergic nociceptive neurons may also significantly contribute to the mechanisms of neurite outgrowth of DRG neurons. These observations suggest distinct regenerative propensity for differing populations of DRG neurons which is significantly affected through insulin receptor signaling.