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ENDOPLASMIC RETICULUM STRESS AND PERIPHERAL PREDIABETIC AND DIABETIC NEUROPATHY
Author(s) -
Obrosova Irina G,
Watcho Pierre,
Maksimchyk Yury,
Shevalye Hanna,
Stavniichuk Roman,
Lupachyk Sergey
Publication year - 2010
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.24.1_supplement.1035.1
Subject(s) - medicine , endocrinology , unfolded protein response , endoplasmic reticulum , peripheral neuropathy , pathogenesis , diabetes mellitus , type 2 diabetes , insulin resistance , prediabetes , chemistry , biochemistry
Endoplasmic reticulum (ER) stress caused by accumulation of unfolded proteins in the ER lumen, contributes to beta‐cell loss, insulin resistance, and plays an important role in the pathogenesis of both Type 1 and Type 2 diabetes. We evaluated the role of this phenomenon in the pathogenesis of prediabetic and diabetic peripheral neuropathy. The experiments have been performed in 1) Zucker lean and Zucker fa/fa rats, a model of obesity and Type 2 prediabetes, and 2) control and STZ‐diabetic rats, a model of Type 1 diabetes. Both 16‐wk‐old Zucker fa/fa rats and STZ‐diabetic rats with 12‐wk duration of STZ‐diabetes displayed ER stress response manifest by overexpression of BiP/GRP78 and GRP94 in the peripheral nerve. They also had nerve conduction velocity (NCV) deficit and small sensory nerve fiber dysfunction. Treatment with the chemical chaperone trimethylamine N‐oxide (TMAO) reversed sensory NCV deficit and alleviated thermal hypoalgesia and tactile allodynia in Zucker fa/fa rats. It also prevented sensory NCV deficit and partially prevented motor NCV deficit and small sensory nerve fiber dysfunction in STZ‐diabetic rats. In conclusion, ER stress is implicated in prediabetic and diabetic peripheral neuropathy. Studies of biochemical mechanisms of ER stress‐induced peripheral nerve damage are in progress.