In vivo peripheral nervous system insulin signaling

• Published in: Journal of the peripheral nervous system 2013-09, Vol.18 (3), p.209-219
• Main Authors: Grote, Caleb W., Ryals, Janelle M., Wright, Douglas E.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Diabetes; Diabetic neuropathy; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Ganglia, Spinal - drug effects; Glucose; Hyperglycemia; Hypoglycemic Agents - pharmacology; Insulin; Insulin - pharmacology; Male; Mice; Mice, Inbred C57BL; neuronal Akt activation; neuronal insulin signaling; peripheral nervous system; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Sciatic Nerve - drug effects; Serine - metabolism; Signal Transduction - drug effects; Threonine - metabolism; Time Factors
• ISSN: 1085-9489; 1529-8027
• DOI: 10.1111/jns5.12033

Alterations in peripheral nervous system (PNS) insulin support may contribute to diabetic neuropathy (DN); yet, PNS insulin signaling is not fully defined. Here, we investigated in vivo insulin signaling in the PNS and compared the insulin responsiveness to that of muscle, liver, and adipose. Non‐diabetic mice were administered increasing doses of insulin to define a dose‐response relationship between insulin and Akt activation in the dorsal root ganglion (DRG) and sciatic nerve. Resulting EC50 doses were used to characterize the PNS insulin signaling time course and make comparisons between insulin signaling in the PNS and other peripheral tissues (i.e., muscle, liver, and adipose). The results demonstrate that the PNS is responsive to insulin and that differences in insulin signaling pathway activation exist between PNS compartments. At a therapeutically relevant dose, Akt was activated in the muscle, liver, and adipose at 30 min, correlating with the changes in blood glucose levels. Interestingly, the sciatic nerve showed a similar signaling profile as insulin‐sensitive tissues; however, there was not a comparable activation in the DRG or spinal cord. These results present new evidence regarding PNS insulin signaling pathways in vivo and provide a baseline for studies investigating the contribution of disrupted PNS insulin signaling to DN pathogenesis.