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Protection from High-fat-diet-induced Impaired Glucose Tolerance in Female Sprague-Dawley Rats

Author: Wang
Tutor: HeFengTian
School: Third Military Medical University
Course: Biochemistry and Molecular Biology
Keywords: High fat diet Male and female rats Impaired glucose tolerance Insulin Resistance Islet function Oxidative Stress
CLC: R587.1
Type: Master's thesis
Year: 2008
Downloads: 111
Quote: 0
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Abstract


Background and Objective: diabetes mellitus (DM) is a major challenge to human health in the 21st century facing the International Diabetes Federation (IDF) in 2003, according to the epidemiological investigation, found that the incidence of diabetes and impaired glucose tolerance were 5.1% and 8.2 %. World there are now more than 240 million people with diabetes, and is growing rapidly every year, is expected by 2025, there are around 380 million diabetes patients. Diabetes is the result of both genetic and environmental factors, impaired insulin resistance (IR) and β-cell function is the incidence of type 2 diabetes mellitus (T2DM) are two important factors, but studies have shown that these two factors in the T2DM preliminary ie impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) has appeared in the stage the crowd. Occurrence in the incidence of diabetes or diabetes, decreased glucose tolerance in the existence of gender differences is not yet entirely clear. Studies have found that in the rat model, which male rats with a high incidence of non-insulin-dependent diabetes mellitus (NIDDM) in female rats. The long-range high-fat diet is one of the important environmental factors induced impaired glucose tolerance and diabetes, has been recognized more and more attention. Such abnormalities associated with insulin resistance and insulin secretion reduce related. Human epidemiological studies found that the food is not limited to the fatty acids in the form of a high-fat diet than people who eat a low-fat diet are more likely to develop abnormal glucose metabolism. Review the relevant literature, we found that there is little experimental study of high-fat diet for both male and female sex, most of the experiments were conducted in men or male animals. However, this sex-specific differences in rodents diabetes is not uncommon. It has been reported found in the NSY rats of 48 weeks of age, 98% of male rats will develop diabetes, while only 31% of the incidence of female rats. Similar to some research pointed out that many of the transgenic male rats with different genetic backgrounds are present with this phenomenon, impaired glucose tolerance in ZDF rats, only ZDF adult obese male rats developed diabetes and is considered study of NIDDM model, while the other ZDF rats, including thin and female rats, are not the development of diabetes, and therefore can not be used as the experimental model of NIDDM. Modan reported NIDDM patients in the study of human-Africa diabetic first-degree relatives of adult men with impaired glucose tolerance in an oral glucose tolerance test, higher than adult women. Despite the existence of gender differences in the type 2 diabetes is still controversial, but there are gender differences in the impact of the high-fat diet metabolism (glucose metabolism). Obesity in women than men, are more common, but a higher incidence of the latter metabolic disorders, including obesity, dyslipidemia, impaired glucose tolerance, type 2 diabetes and hypertension. Mechanism causing these gender differences also need to conduct more in-depth research. Long-range high-fat diet in order to study the impact of inter-gender differences in male and female rats with impaired glucose tolerance, this study uses a simple high-fat diet fed a normal SD rats for up to 14 months, the dynamic observation of long-range high-fat SD male and female rats glucose metabolism the influence and impaired glucose tolerance in the process, to explore possible mechanisms of resistance to high-fat induced impaired glucose tolerance in female rats. Materials and Methods: The entire study we examined the long-range impact of the high-fat diet on normal SD rats glucose metabolism. 1, the application of high fat diet fed a normal SD rats for up to 14 months to establish the rat model of impaired glucose tolerance and insulin resistance. 2, the conventional method to detect changes in body weight of rats in each group and the fasting blood glucose and lipid metabolism indicators; paraffin sections of HE staining of liver lipid deposition. 3, respectively, in the first 5,10,14 months intraperitoneal injection of glucose tolerance test (were performed to) the detection of impaired glucose tolerance. 4, the determination of the 14 months of fasting insulin, insulin resistance index, detection of male and female rats early insulin secretory function. 5, the determination of the 14-month rat liver, muscle and pancreas tissue homogenates mitochondrial and microsomal malondialdehyde (MDA), glutathione (GSH) and peroxide and catalase (CAT) content detect mouse liver, muscle and pancreas tissue oxidative stress and anti-oxidative stress levels. Results: 1, in the feeding of 1 to 5, high-fat group of male and female rats fasting glucose than normal diet group were significantly higher (p lt; 0.05), and thereafter the difference was not significant. 2, IPGTT, high fat diet for two hours in the first 5 to 10 months in male rats after glucose load blood glucose (2h PG) than the S \u0026 P food group significantly decreased, to 14 months were impaired (2h PG gt; 7.8mmol / L), and from 5 to 14 months throughout the experiment, 2h PG between the high-fat group of female rats with normal diet group without significant difference. 3, 14 months, high-fat male rats, fasting insulin levels were significantly higher than the fat female rats (p lt; 0.05), while no significant differences between male and female general food group. Fat male rats, the level of insulin resistance (HOMA-IR) was also significantly higher than the fat female rats (p lt; 0.05), and HOMA-IR between male and female general food group no significant differences. 4, the high-fat group of male rats FFA levels in the first 5, 7.5 months were higher than female hyperlipidemic rats, especially in the 7.5 months when there is a significant difference (p lt; 0.01). 5 early insulin secretion function of female rats after long-range high-fat feeding significantly higher than that in male rats (p lt; 0.05). The group of female rats and fat liver, muscle tissue MDA levels are lower than the high-fat group of male rats, CAT levels are higher than male rats high-fat group, a significant difference (p lt; 0.05 to 0.01). Pancreatic tissue MDA levels of the high-fat group of female rats was also lower than the high-fat group of male rats, CAT, GSH levels were higher than male rats high-fat group, but no significant difference. Conclusion: 1, impaired glucose tolerance induced by the high fat diet alone there are significant gender differences in the phenomenon: male rats glucose tolerance loss occurs early, significant changes, suffer in the end; female rats tolerance changes occur slowly than light, and not ultimately reach the extent of damage, i.e. the female having the role of impaired glucose tolerance induced resistance hyperlipidemia. 2 female resistance to high-fat induced impaired glucose tolerance mechanisms comes from two aspects: on the one hand, the degree of peripheral insulin resistance than the male the fat rat light; hand, β-cell function in male hyperlipidemic rats . 3, the long-range high fat diet for the degree of insulin resistance in female rats was significantly lower than in male rats, with plasma free fatty acid levels and liver and muscle tissue levels of oxidative stress than male rats is related to the low. 4, fat female rat pancreatic β-cell function better than the fat of male rats, lipotoxicity and pancreatic tissue free fatty acids may lower the level of oxidative stress related.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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