Abstract
Insulin, besides its pivotal role in energy metabolism, may also modulate neuronal processes through acting on insulin receptors (InsRs) expressed by neurons of both the central and the peripheral nervous system. Recently, the distribution and functional significance of InsRs localized on a subset of multifunctional primary sensory neurons (PSNs) have been revealed. Systematic investigations into the cellular electrophysiology, neurochemistry and morphological traits of InsR-expressing PSNs indicated complex functional interactions among specific ion channels, proteins and neuropeptides localized in these neurons. Quantitative immunohistochemical studies have revealed disparate localization of the InsRs in somatic and visceral PSNs with a dominance of InsR-positive neurons innervating visceral organs. These findings suggested that visceral spinal PSNs involved in nociceptive and inflammatory processes are more prone to the modulatory effects of insulin than somatic PSNs. Co-localization of the InsR and transient receptor potential vanilloid 1 (TRPV1) receptor with vasoactive neuropeptides calcitonin gene-related peptide and substance P bears of crucial importance in the pathogenesis of inflammatory pathologies affecting visceral organs, such as the pancreas and the urinary bladder. Recent studies have also revealed significant novel aspects of the neurotrophic propensities of insulin with respect to axonal growth, development and regeneration.
Highlights
Insulin is a major hormone regulating the energy metabolism of the organism
Characterization of the chemical phenotypes of primary sensory neurons (PSNs) have revealed the sensitivity to insulin and the localization of insulin receptors (InsRs) in a sizeable subpopulation of neurons amounting to about 60 per cent of spinal PSNs of unidentified target identity [19,22,23] Further, it has been demonstrated that insulin and insulin-like growth factor 1 (IGF-1) can sensitize the transient receptor potential vanilloid 1 (TRPV1) receptor [19]. These findings suggested a possible interplay among insulin, InsR and TRPV1 receptor in PSNs under pathophysiological conditions
Experimental evidence indicates a pivotal role of TRPV1 receptor expressing PSNs in the pathomechanism of acute pancreatitis
Summary
Insulin may modulate distinct neural functions through insulin receptors (InsRs) expressed in neurons of the central and peripheral nervous system. Neuronal localizations of insulin and InsRs have been first described in the central nervous system mostly in areas involved in the regulation of energy balance and food intake [1]. Later studies disclosed widespread brain distribution of InsRs [1,2,3,4], and that of insulin, which is of peripheral (plasma) rather than neuronal origin [5]. The Akt cascade is involved in the translocation of the glucose transporter 4 into the plasma membrane, regulation of glycogen, protein and lipid synthesis and glucose intake, while MAPK is related to the modulation of gene expression, proliferation and cell growth [11,12,13,14].
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