Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy.
Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause-effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.
Department of Endocrinology, The General Hospital of the PLA Rocket Force, Beijing 100088, China. ylynn1028@126.com.
Linlin
L
Yang
Department of Endocrinology, The General Hospital of the PLA Rocket Force, Beijing 100088, China. liqm0806@163.com.
Quanmin
Q
Li
Department of Endocrinology, The General Hospital of the PLA Rocket Force, Beijing 100088, China. xinming2211@126.com.
Xinming
X
Liu
Department of Endocrinology, The General Hospital of the PLA Rocket Force, Beijing 100088, China. tommy19921030@126.com.
Shiguang
S
Liu
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000378:metabolism*; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D062552:NAV1.3 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
NaV1.3; NaV1.7; diabetes mellitus; dorsal root ganglion neurons; painful diabetic neuropathy; pancreatic islet cells