Molecular Study On Expression And Regulation Mechanisms Of Orexin/Leptin In Insulin Resistance Animal Model

It is Insulin resistance that the insulin is not to bring into full play effect under normal contraption, because the effect of insulin decreased on intape and clearing glucose in peri-constitution.Obesity cause abnormal constitution and expression of insulin receptor, therefore, there is Insulin resistance in adipose tissue. IR would induce adipo-sis, diabetes mellitus, hypertensive disease, Atherosclerosis, abnormality of lip-id metabolism and so on. Orexin, a neuropeptide found in 1998, has been shown of being involved in many physiological progresses such as regulation of food intake, sleep, and in response to acute stress through its receptors orexin 1 receptor and orexin 2 receptor. The achievement of introduction of orexin together with the introduction of obese gene ( ob gene) and its encoding protein leptin in 1994s, has been well recognised as step Stones in the field of obese research. Therefore, In this study, we aimed to study on at expression and regulation mechanisms of Orexin/Leptin in insulin resistance animal model.Section A. Evaluation of Insulin resistance rat model and euglycaemic clamping induced by high fat or fructose dietObjectiveIn order to research the Orexin/Leptin, Evaluation of Insulin resistance rat model would confirm by hyperinsulinemic egulycemic clamp technique. The model employed in this study with abnormal diet intake has been verified by the internationally recognised gold standard euglycaemic clamping in way of evaluating the sensitivity of insulin.Methods60 male Wistar rats weighing between 200 and 250 grams were grouped into A and B randomly in representative of control group (A) with access freely to normal commercial rat food, and experiment group { B and C) which high fructose diet and high fat diet with carbon ratio of 10% and essential vitamins and minerals were given. Energy intake 310 KJ per day was ensured and 4 weeks after feeding rats were evaluated for euglycaemic clamping and further experiments. Euglycaemic clamping evaluation; Five rats from each group (A and B) were cannulated via carotid arteries bilaterally connected to syringes filled with heparin saline. Bilateral femoral veins cannulations connected to infusion pumps of insulin and 10% glucose solution. Evaluation; GIR60-1, the mean (M) of those 13 GIR obtained from the 60th minute to the 120 th minute, was used as an indicator of insulin resistance with interpretation of lower the GIR60-120 indicating more severe insulin resistance.ResultsBody weight, blood glucose, insulin, triglyceride in group B were all higher than those in group A after 4 week high fructose diet feeding ( p < 0.05 or p < 0. 01) , indicating significant changes of body weight and related biochemical parameters of rats in group B at the time when insulin resistance developed ( Table 1 and 2).ConclusionsThe model employed in this study with a high fructose and fat diet intake has been verified by the internationally recognised gold standard euglycaemic clamping in way of evaluating the sensitivity of insulin. We have found the utilise of this model is possibly superior to convenient genetic and drug induced models in studying the mechanism of insulin resistance in respects of including environmental interfering factors into consideration, i. e. the controllable factors as those factors are of important of incidence and developing insulin resistance. It has been reported that up to 4 weeks feeding in which of 35% of total energy provided from fructose for rats, insulin sensitivity could be severely impacted in liver and peripheral tissues and GIR60-120 in 5-12mg . kg-1. min-1. This effect is characterised by a time difference in which there is an improvement of glucose metabolism in the first two weeks but impact will appear for over 4 weeks feeding.Section B. Orexin/Leptin system in insulin resistance rat model induced by high-fructose and high-fat dietObjectiveInsulin resistance is the common risk factor for adiposis, diabetes mellitus type 2 . In this study, we aimed at those regulating...