| Abstract: |
Changes in lifestyle and diet have resulted in an increased number of obese subjects. Obesity is currently an important causative factor of health-related problems as diabetes mellitus, cardiovascular diseases, cancer, and others. The possibility of preventing the onset of diabetes using herbal medicines, as mulberry and others has recently attracted more attention.In this work, the prophylactic and the therapeutic effect of mulberry leave extract and acarbose, on HF-induced obesity and insulin resistance in rats have been studied. The prophylactic effect was investigated by co-administration of both drugs for 60 days concurrently with the high fat diet. Also, in this study we investigated the effect of mulberry leaves extract and acarbose in the management of T2DM associated with obesity by co-administration of both drugs for 45 days concurrently with high fat diet to obese diabetic insulin resistant rats.To achieve this goal, blood glucose, serum insulin and oral glucose tolerance were determined, while insulin resistance index and the ?-cell function % were calculated. In addition, serum levels of triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and free fatty acids were also measured to give us a picture about the effect of high fat diet and the effect of drugs used in this study on fatty acid oxidation and lipolysis.Moreover, we tried to investigate the antioxidant effect of the used drugs on the oxidative damage caused by HF diet induced-obesity by measuring glutathione content, glutathione peroxidase and superoxide dismutase enzyme activities.To solve the mystery about the effect of HF diet and mulberry leaves extract on muscle glucose uptake and utilization and its relation to insulin resistance, isolated diaphragm method was used.Besides, in the present work, we investigated sucrase enzyme inhibition by co-administration of sucrose with each of mulberry leaves extract or acarbose to either normal or obese diabetic insulin resistant rats.The results obtained can be summarized as follow:1- Effects of high fat diet:1- Feeding rats with HF diet resulted in obesity, insulin resistance and diabetes as shown by the significant elevation in serum levels of glucose, insulin, and insulin resistance index. The serum levels of triglyceride, total cholesterol, LDL-C, and FFAs were also measured. On the other hand, there was a significant reduction in HDL-C and ?-cell function %. Moreover feeding with HF diet is associated with decreased antioxidant capacity as indicated by the reduction in glutathione content, and glutathione peroxidase enzyme activity.2- HF diet induced glucose intolerance, reduced glucose utilization as indicated by the increase in the area under the oral glucose tolerance curve. Furthermore, HF diet is associated with impaired insulin-stimulated glucose uptake in muscles as evident by the significant decrease in glucose uptake by diaphragms isolated from obese rats. These results indicating that rats fed with HF diet exhibited decreased muscle glucose uptake, glucose utilization and overall glucose disposal rate.2- Effect of mulberry leaves extract as prophylactic and treatment therapies:1- Intraperitonial and oral administration of mulberry leaves extract (100 mg/kg) as a protective therapy and treatment therapy to obese diabetic insulin resistant rats concurrently with high fat diet induced a significant reduction in serum glucose and insulin levels and insulin resistant index indicating an improved insulin action. In addition, mulberry significantly decreased the levels of TG, TC, LDL-C and FFAs.2- Mulberry administration induced significant increase in the ?-cell function , HDL-C level, glutathione content and antioxidant enzymes activities as glutathione peroxidase and superoxide dismutase.3- Mulberry significantly increased the area under glucose tolerance curve, and muscle glucose uptake either in normal or in obese diabetic insulin resistant rats, in both the presence and the absence of insulin. So mulberry therapy improves glucose uptake, utilization and overall glucose disposal.4- Mulberry significantly increased improved of insulin resistance state and diabetes associated with high fat diet.3-Effect of acarbose as prophylactic and treatment therapies:1- Oral administration of acarbose (200 mg/kg) as a protective therapy and treatment therapy to obese diabetic insulin resistant rats concurrently with high fat diet induced a significant reduction in serum levels of glucose and insulin and insulin resistant index. In addition, acarbose significantly decreased the levels of triglyceride, total cholesterol, LDL-C and free fatty acid.2- Acarbose administration induced significant increase in the area under glucose tolerance and ?-cell function %. In addition, it induced significant increase in the of HDL-C serum level.3- Acarbose did not cause a significant change in antioxidant enzymes, glutathione content, and glutathione peroxidase, in prophylactic and treatment therapies and superoxide dismutase in treatment therapy.4- Effects of mulberry leave extract and acarbose on alpha glucosidase enzyme activity:Administration of mulberry leaves extract and acarbose along with sucrose (2gm/kg) in normal and obese diabetic insulin resistant rat induced significant reduction in the blood glucose level and in the area under glucose curve after sucrose loading. Such reduction indicating reduced glucose utilization and lowering of alpha glucosidase activity (sucrase enzyme). However acarbose has a more pronounced alpha glucosidase inhibition than mulberry leaves extract.In light of the results of the present study it could be concluded that:1- Obesity induced by high fat diet participates in the incidence of insulin resistance and T2DM. This effect may be attributed to the excessive fatty acid oxidation, the induced oxidative stress and reduced muscle glucose uptake and utilization.2- Mulberry leaves extract delayed the incidence of obesity induced diabetes mellitus. This effect may be attributed to its ability to protect both the pancreas and the liver against free radicals produced by elevated glucose and FFAs.3- The progressive reduction in serum lipids specially FFAs and the increase in antioxidant enzymes may lead to the improvement of glucose tolerance, insulin sensitivity and decreased blood glucose level. These results indicate that oxidative stress may be implicated in the pathogenesis of obesity induced type 2 diabetes mellitus.4- Mulberry leaves extract delayed the incidence of HF diet induced muscle insulin resistance. This effect may be attributed to its ability to increase muscle glucose uptake.5-Acarbose delayed the progression of diabetes mellitus as a protective therapy. As a treatment therapy, acarbose improved the diabetic state, insulin sensitivity and lipids profile. However acarbose therapy did not affect antioxidant state of experimental rats.6- Both mulberry leaves extract and acarbose inhibit alpha glucosidase enzymes activity as indicated by their inhibition of sucrase enzyme activity.7-Depending on our findings, it seems that mulberry could be useful in the management of T2DM. Further clinical investigations are needed to confirm its effect such as improvement of insulin action, release and increased muscle glucose uptake.
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