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Desensitization of TRPV1 receptor in the hypothalamus of type 1 diabetic mice
Author(s) -
Zsombok Andrea,
Gao Hong,
Miyata Kayoko,
Hebert K. Doug,
Bhaskaran Muthu D.,
Derbenev Andrei V
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1062.13
Subject(s) - endocrinology , medicine , trpv1 , receptor , hypothalamus , agonist , desensitization (medicine) , insulin receptor , homologous desensitization , chemistry , insulin , biology , insulin resistance , transient receptor potential channel
Preautonomic neurons in the paraventricular nucleus (PVN) of the hypothalamus regulate sympathetic and parasympathetic output to the liver participating in the regulation of hepatic glucose production. Recently, peripheral TRPV1 receptor (transient receptor potential vanilloid type 1) involvement in the regulation of energy and fat metabolism was discovered. However, the role of central TRPV1 on glucose metabolism is unclear. We revealed TRPV1 receptor and insulin receptor substrate 2 (IRS2) protein expression levels in control and type 1 diabetic (T1D) mice by using Western blot. Patch‐clamp recordings from control and T1D mice were performed to characterize synaptic properties of liver‐related PVN neurons identified with PRV‐152. Administration of capsaicin, a TRPV1 receptor agonist increased mEPSCs frequency in liver‐related PVN neurons in control but not in T1D mice. There was no difference in total TRPV1 receptor protein expression, however increased phosphorylation of TRPV1 receptor was observed in T1D mice, suggesting acute desensitization of TRPV1 receptor. Additionally, decreased IRS2 expression level was detected in the hypothalamus of T1D mice. Therefore, T1D appears to affect TRPV1 receptor signaling contributing to autonomic dysfunction and dysregulation of glucose metabolism. Supported by AHA 10GRNT4540000, Tulane BIRCWH 2K12HD0434451, NHLBI R21HL091293, R21HL091293‐01A1S1.