Atherogenic diet induced diabetes mellitus: Involvement of thyroid hormones Hamendra Singh Parmar ⁎ , Anand Kar Thyroid Research Unit, School of Life Sciences, D.A. University, Takshashila Campus, Indore-452017, India Received 19 December 2006; received in revised form 6 June 2007; accepted 7 June 2007 Available online 27 June 2007 Abstract An investigation was made to reveal the possible involvement of thyroid hormones in the progression of diabetes mellitus in response to an atherogenic diet; CCT (4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil). Following the intake of CCT diet for 14 consecutive days a decrease in the serum levels of insulin, both the thyroid hormones, triiodothyronine (T 3 ) and thyroxine (T 4 ); hepatic glycogen content, hepatic type-1 iodothyronine 5′-mono-deiodinase (5′D) and serum α-amylase activities were observed, while there was an increase in the levels of serum glucose and nitrite and in lipid peroxidation of heart, liver and kidney tissues as well as in serum. However, simultaneous administration of L- thyroxine (500 μg/kg/day, s.c.) to CCT-diet fed animals resulted in the amelioration of all the aforesaid adverse changes including that of serum glucose, insulin, α-amylase, hepatic glycogen content and nitrite levels, suggesting the involvement of thyroid hormones in the progression of CCT-diet induced diabetes mellitus. © 2007 Elsevier B.V. All rights reserved. Keywords: Insulin; Glucose; Thyroid hormones; Glycogen; α-amylase; Diabetes mellitus 1. Introduction Diabetes mellitus is a major health problem worldwide. This metabolic disorder is characterized by hyperglycemia and disturbances in carbohydrate, protein and fat metabolisms, which may be secondary to an absolute or relative lack of the hormone insulin (Alberti and Zimmet, 1998). In fact, the number of people in the world with diabetes has increased dramatically over recent years and by 2010 it has been estimated that the diabetic population will increase to 221 million around the world (Carter, 2004). Very often it is the result of insulin resistance which is closely associated with hypercholesterolemia and/or obesity, the latter being more true for type-2 diabetes mellitus (Hirosumi et al., 2002). It is also well established that thyroid hormones have major influence on carbohydrate and lipid metabolisms (Muller and Seitz, 1984a,b; Ganong, 2005). In fact, hypothyroidism is not only known to induce hypercholesterolemia and obesity, but also it diminishes insulin secretion (Diaz et al., 1993; Iossa et al., 2001; Duntas, 2002).Recently our laboratory has reported hyperglycemia and hypothyroidism following the intake of hypercholesterolemic diet CCT (4% cholesterol, 1% cholic acid and 0.5% 2-thiuracil, Jatwa and Kar, 2006). However, despite the fact that lipid and glucose metabolism are dependent on thyroid hormones (Ganong, 2005), the involvement of thyroid hormones in the progression of diabetes mellitus in response to CCT-diet, if any, was not worked out till date. Therefore, in the present investigation an attempt has been made to reveal the diabetogenic changes and their amelioration by exogenous L- thyroxine administration to CCT-diet fed male rats. The major parameters considered in this study were serum levels of glucose, insulin, triiodothyronine (T 3 ), thyroxine (T 4 ), α- amylase, nitrite concentration and hepatic glycogen content and hepatic type-1 iodothyronine 5′-mono-deiodinase (5′D) activity. In addition, some other supporting parameters such as; change in body weight (%), tissue lipid peroxidation, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low- density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and atherogenic index have also been studied, all being related to thyroid functions (Diaz et al., 1993; Lee et al. 1994; Duntas, 2002; Claxton and Brands, 2003; Tahiliani and Kar, 2003; Jatwa and Kar, 2006). European Journal of Pharmacology 570 (2007) 244 – 248 www.elsevier.com/locate/ejphar ⁎ Corresponding author. Tel.: +91 731 2477166; fax: +91 731 2360026. E-mail address: hamendrasingh999@yahoo.co.in (H.S. Parmar). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.06.020