TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes.
Document Type
Article
Publication Date
2006
Keywords
Autoimmunity, Capsaicin, Diabetes-Mellitus-Type-1, Female, Inflammation, Insulin-Resistance, Insulin-Secreting-Cells, Islets-of-Langerhans, Male, Mice, Mice-Congenic, Mice-Inbred-C57BL, Mice-Inbred-NOD, Neurons-Afferent, Substance-P, T-Lymphocytes, TRPV-Cation-Channels
First Page
1123
Last Page
1135
JAX Source
Cell 2006 Dec; 127(6):1123-35.
Abstract
In type 1 diabetes, T cell-mediated death of pancreatic beta cells produces insulin deficiency. However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear. We report that TRPV1(+) pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1(+) neurons are eliminated. TRPV1(NOD), localized to the Idd4.1 diabetes-risk locus, is a hypofunctional mutant, mediating depressed neurogenic inflammation. Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1(-/-) mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data uncover a fundamental role for insulin-responsive TRPV1(+) sensory neurons in beta cell function and diabetes pathoetiology.
Recommended Citation
Razavi R,
Chan Y,
Afifiyan FN,
Liu XJ,
Wan X,
Yantha J,
Tsui H,
Tang L,
Tsai S,
Santamaria P,
Driver JP,
Serreze D,
Salter MW,
Dosch HM.
TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes. Cell 2006 Dec; 127(6):1123-35.