α-Tocopherol Status and Altered Expression of α-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models

Abstract

Vitamin E is a fat-soluble antioxidant that comprises 4 tocopherols (a-, b-, g-, and d-) and 4 tocotrienols (a-, b-, g-, and d-). Of all these vitamin E subtypes, a-tocopherol is the most well-known for its antioxidant activity (1). Lipid-soluble vitamin E has a critical role as an antioxidant protecting the lipids of the plasma membranes and lipoproteins from peroxidation. Dietary vitamin E, including tocopherols and tocotrienols, which are components of bile salt micelles, is absorbed in the intestine. Vitamin E, along with lipids, is incorporated into nascent chylomicrons within the enterocyte, and these chylomicrons are then secreted into the lymphatics and blood vessels (2). After transporting dietary lipids to other locations in the body, chylomicrons are returned to and taken up by the liver. In the liver, a-tocopherol selectively binds to a-tocopherol transfer protein (a-TTP) and is incorporated into very low-density lipoproteins (VLDL). a-TTP is a hepatic cytosolic protein, which facilitates the transport of a-tocopherol to the plasma membrane for the secretion of a-tocopherol into VLDL (1). a-TTP has a critical role in maintaining circulatory a-tocopherol levels. a-TTP gene disrupted mice reveal markedly reduced plasma a-tocopherol levels; moreover, the mutation of the human a-TTP gene is responsible for ataxia with vitamin E deficiency (1, 2). The ATPbinding cassette transporter-1 (ABCA-1), which transports cholesterol and phospholipids, facilitates the secretion of a-tocopherol in the plasma membrane. VLDL, including a-tocopherol, in circulation is lipolysed into low-density lipoprotein (LDL) by lipoprotein lipase, and this LDL is taken up into the peripheral tissues via the action of the LDL receptor. The mechanism of a-tocopherol metabolism has been recently determined (2). The catabolism of tocopherols and tocotrienols is mediated by cytochrome P450 4F2 (CYP4F2), and the resulting metabolite, carboxyethyl hydroxychroman (CEHC), is excreted in urine as glucuronic conjugates.Diabetes is a metabolic disorder pertaining to glucose uptake due to a lack of insulin production by pancreatic b-cells (type 1 diabetes), or it manifests as peripheral insulin resistance, including adipose tissue and muscles (type 2 diabetes). The production of reactive oxygen species (ROS) is the major pathogenesis of diabetes and its complications. Hyperglycemia leads to an increased release of ROS in peripheral tissues (3). In experimental studies, vitamin E supplementation improved the Summary Vitamin E plays a critical role as an antioxidant in several pathological conditions, including diabetes, cancer, cardiovascular diseases, and neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to the lack of adequate insulin production (type 1) or peripheral insulin resistance (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and its complications. The purpose of the present study was to determine a-tocopherol status and the expression of a-tocopherol-related proteins, including ...

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