Insulin as an in vivo growth factor

• Published in: Experimental neurology 2004-07, Vol.188 (1), p.43-51
• Main Authors: Xu, Q.-G., Li, X.-Q., Kotecha, S.A., Cheng, C., Sun, H.S., Zochodne, D.W.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - pharmacology; Biological and medical sciences; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Growth Cones - drug effects; Growth Cones - metabolism; Growth Cones - ultrastructure; Growth Substances - metabolism; Growth Substances - pharmacology; Insulin - metabolism; Insulin - pharmacology; Insulin receptors; Male; Medical sciences; Mice; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - metabolism; Muscle, Skeletal - innervation; Muscle, Skeletal - physiopathology; Nerve Fibers, Myelinated - drug effects; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - ultrastructure; Nerve injury; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons, Afferent - cytology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neuropharmacology; Neuroprotective agent; Peripheral nerve; Peripheral Nerves - drug effects; Peripheral Nerves - growth & development; Peripheral Nerves - metabolism; Pharmacology. Drug treatments; Receptor, IGF Type 1 - drug effects; Receptor, IGF Type 1 - metabolism; Receptor, Insulin - antagonists & inhibitors; Receptor, Insulin - metabolism; Regeneration; Sciatic Neuropathy - drug therapy; Sciatic Neuropathy - metabolism; Sciatic Neuropathy - physiopathology; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2004.03.008

Insulin peptide has been identified to promote regeneration of axons in culture and in some in vivo model systems. Such actions have been linked to direct actions of insulin, or to cross occupation of closely linked IGF-1 receptors. In this work, we examined insulin support of peripheral nerve regenerative events in mice. Systemic insulin administration accelerated the reinnervation of foot interosseous endplates by motor axons after sciatic nerve transection and enhanced recovery of functional mouse hindpaw function. Similarly, insulin accelerated the regeneration-related maturation of myelinated fibers regrowing beyond a sciatic nerve crush injury. That such benefits might occur through direct signaling on axons was supported by immunohistochemical studies of expression with an antibody directed to the β insulin receptor (IR) subunit. The proportion of sensory neurons expressing IRβ increased ipsilateral to a similar sciatic crush injury in the L4 and L5 dorsal root ganglia. Insulin receptors, although widely expressed in axons, were also preferentially and intensely expressed on axons regrowing just beyond a peripheral nerve crush injury zone. The findings indicate that insulin imparts a substantial impact on regenerating peripheral nerve axons through upregulation of its expression following injury. Although the findings do not exclude insulin coactivating IGF-1 receptors during regeneration, its own receptors are present and available for action on injured nerves.