title: Proanthocyanidins protect against early diabetic peripheral neuropathy by modulating endoplasmic reticulum stress.
abstract: Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of type 2 diabetes mellitus (T2DM). Recent findings reveal an important role of endoplasmic reticulum (ER) stress in the development of DPN and identify a potential new therapeutic target. Schwann cells (SC), the myelinating cells in peripheral nervous system, are highly susceptible to ER homeostasis. Grape seed proanthocyanidins (GSPs) have been reported to improve DPN of type 1 diabetic rats and relieve ER stress in skeletal muscles and pancreas of T2DM. We investigated the potential role of ER stress in SC in regulating DPN of T2DM and assessed whether early intervention of GSPs would prevent DPN by modulating ER stress. The present study was performed in Sprague-Dawley rats made T2DM with low-dose streptozotocin and a high-carbohydrate/high-fat diet and in rat SC cultured in serum from type 2 diabetic rats. Diabetic rats showed a typical characteristic of T2DM and slowing of nerve conduction velocity (NCV) in sciatic/tibial nerves. The lesions of SC, Ca(2+) overload and ER stress were present in sciatic nerves of diabetic rats, as well as in cell culture models. GSPs administration significantly decreased the low-density lipoprotein level and increased NCV in diabetic rats. GSPs or their metabolites also partially prevented cell injury, Ca(2+) overload and ER stress in animal and cell culture models. Therefore, ER stress is implicated in peripheral neuropathy in animal and cell culture models of T2DM. Prophylactic GSPs treatment might have auxiliary preventive potential for DPN partially by alleviating ER stress.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, PR China. Electronic address: liyongbmu@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D056604:Grape Seed Extract / Q000627:therapeutic use*; D008297:Male; D044945:Proanthocyanidins / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects*; D012584:Sciatic Nerve / Q000473:pathology
chemical_list: D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins
keywords: Calcium; Diabetes; Endoplasmic reticulum stress; Neuroprotection; Proanthocyanidins; Schwann cells