Med. J. Cairo Univ., Vol. 87, No. 6, September: 3673-3685, 2019 www.medicaljournalofcairouniversity.net Vit D3 versus L Carnitine Supplement in Alleviating Age-Related Insulin Resistance in A Naturally Aging Rat Model ISLAM I. HEGAB, M.D.* and MARWA M. ATEF, M.D.** The Departments of Physiology* and Biochemistry**, Faculty of Medicine, Tanta University, Egypt Abstract Background: Insulin Resistance (IR) has long been rec- ognized as a characteristic of aging. Many studies recorded beneficial roles of Vitamin D3 (VD3) and L-Carnitine (LC) in obesity and type 2 diabetes. Aim of Study: To evaluate the role of VD3 versus LC in attenuating the age-related IR in a naturally aging rat model, clarifying their possible underlying mechanisms. Material and methods: Rats were divided into 4 groups; Young Control (YC), aged group, VD3-treated aged group (VD3-aged) and LC-treated aged group (LC-aged). Experi- mental procedures included measurement of body weight, Body Mass Index (BMI) and Oral Glucose Tolerance Tests (OGTT). The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index was also calculated. Assays of fasting serum glucose and insulin levels as well as serum tumor necrosis factor- a (TNF- a ), interleukin-6 (IL-6) and adiponectin levels were performed. Moreover, skeletal muscle Sirtuin-1 (SIRT-1), Triglycerides (TGs) and TNF- a levels alongside with the glucose transporter-4 (GLUt4) mRNA expression were assessed. Results: Compared to YC rats, aged rats exhibited signif- icant increase in fasting serum insulin and HOMA-IR as well as an abnormal OGTT. Serum TNF- a and IL-6 levels were significantly increased, whereas serum adiponectin level was significantly decreased in old rats. Furthermore, the SIRT1 levels and GLUT 4 mRNA expression were significantly lower, whereas the TGs and TNF- a were significantly higher in skeletal muscle of aged rats compared to YC ones. On the other hand, these parameters, were equally and significantly attenuated in VD3 and LC supplemented rats compared to non-treated age matched group, except for the skeletal muscle SIRT-1 level which could be elevated only by VD3, while the anti-inflammatory and TGs lowering effects of LC were more prominent than VD3. Nevertheless, the overall effect of VD3 and LC on IR-related parameters were nearly equal. Conclusion: Both VD3 or LC administrations were equally effective in alleviating the age-related IR, thus may provide a possible therapeutic intervention in the aging population. Correspondence to: Dr. Islam I. Hegab, The Department of Physiology, Faculty of Medicine, Tanta University, Egypt Key Words: Vitamin D3 – L-carnitine – Insulin resistance – Aging – Proinflammatory cytokines – Adiponectin – SIRT-1 – GLUT 4. Introduction OVER the few last decades, there has been a robust increase in the number of aging populations with metabolic disorders [1] . Glucose tolerance increas- ingly deteriorates with advancing age leading to high prevalence of impaired glucose tolerance and type 2 diabetes in elderly [2] . Such impairment is primarily as a result of decreased insulin sensitivity coincide with diminished glucose utilization by peripheral tissues, a condition of what so called, Insulin Resistance (IR) [3] . Insulin resistance has been long recognized as a characteristic of aging in human and rodents [4] . Thereby, aging has been considered as a main risk factor for development of metabolic syndrome [5] . Insulin resistance could be increased with age in relation to several well- known age-related changes, including hormonal changes, increased oxidative stress and inflamma- tion [6] . Chronic, low-grade, systemic inflammation is widely accepted as a significant risk factor underlying aging and age-related type 2 diabetes [7] . Additionally, ageing-related IR usually presents low circulating levels of adiponectin [1,8] . Adi- ponectin, an adipocytokine secreted from adipose tissue, is involved in diverse biological processes, including sensitization of the insulin receptor signaling pathway, suppressing inflammation, and triggering the mitochondria biogenesis [9] . The skeletal muscle is regarded as the major site of IR in obesity and type 2 diabetes in elderly individuals [10] . During the ageing process, there is a gradual loss of the capability to adapt changing environments, alongside with excessive flux in fatty acids and impairment of fatty acids oxidation that are usually associated with development of 3673