Effect Of Long-term High-fat Diet On Morphology And Function Of Pancreatic Islet β Cell In Rats

Objective:To explore the effect of long-term high-fat diet on the morphology and function of pancreatic isletβcell in rats in order to provid important clues and more experimental bases,for further study of the pathogenesis of type 2 diabetes mellitus and the correlation of the nutritional factors（fat）and type 2 diabetes mellitus.Methods:1.A total of 128 male rats were randomly divided into control group（n=25）,high-fat group（n=38）and model group（n=65）.Rats in the control group were fed with ordinary diet,and others with high-fat diet.At 8^th week after experiment,rats in the model group received an intraperitoneal injection of 30 mg/kg STZ and rats in the control and high-fat group received an intraperitoneal injection of equal dose of acidified saline.At 10^th week,the model group was divided into diabetic model（n=23）and non-diabetic model group（n=38）according to the level of fasting blood glucose and the high-fat group was randomly divided into high-fat 1 group（n=22）and high-fat 2group（n=16）again.Rats in the diabetic model,non-diabetic model and high-fat 1 group continued to be fed with high-fat diet,while those in the high-fat 2 group with ordinary diet.2.Body weight and fasting blood glucose were detected and intraperitoneal glucose tolerance test was performed at 8^th,10^th,12^th,14^th,16^th,18^th and 20^thh week.Total cholesterol,triglycerides and free fatty acids were measured at 8^th,10^thh and 20^thh week.In addition,fasting serum insulin,insulin sensitivity index and HOMA-insulin resistance were also determined,the pancreata were removed after excision,the insulin immunohistochemistry of pancreas sections was performed and the total volumes of pancreatic islet and the ratio of immune positive areas in pancreatic islet were estimated with stereological methods at 10^thh and 20^thh week.Result:1.The level of fasting blood glucose of the high-fat 1 group was significantly increased by 30.4%at 20^th week compared with that at 10^thh week.The level of fasting blood glucose was significantly higher than that of the control group but lower than that of the diabetic model group in the high-fat 1group at 20^th week.There were 1/3,3/5,4/17,4/17,7/16 and 5/16 rats with the impaired glucose tolerance respectively in the high-fat 1 group each week.The insulin sensitivity index of the high-fat 1 group was significantly lower than that of the control group.The HOMA-IR of the high-fat 1 group was significantly increased 22.8%at 20^th week compared with that at 10^th week.The HOMA-IR was significantly higher than that of the control group but lower than that of the diabetic model group in the high-fat 1 group at 20^thh week.Most of the pancreas islets were similar to that of the control group and few of the pancreas islets at 20^thh week were similar to that of the diabetic model group in the morphological structure in the high-fat 1 group.There were no significant differences in the total volumes of pancreatic islet and the ratio of immune positive areas in the pancreatic islet between the control and the high-fat 1 group,but the total volumes of pancreatic islet and the ratio of immune positive areas in the pancreatic islet of the high-fat 1 group were significantly higher than that of the diabetic model group.2.The level of fasting blood glucose of the high-fat 2 group was significantly lower than that of the high-fat 1 group at 20^th week.There were1/7,1/5,1/5 and 1/12 rats with impaired glucose tolerance respectively in the high-fat 2 group each week.Compared with the high-fat 1 group,the average blood glucose level at 2 hours was significantly decreased 23.2%and 20.5%respectively in the high-fat 2 group at 12^th and 18^th week.Compared with the high-fat 1 group,the HOMA-IR was significantly reduced by 21.6%and the insulin sensitivity index was significantly increased by 3.9%in the high-fat 2group at 20^th week.All pancreas islets were similar to that of the control group in the morphological structure in the high-fat 2 group.The total volumes of pancreatic islet of the high-fat 2 group was significantly increased by 30.5%at 20^thh week compared with that at 10^th week.Compared with the high-fat 1 group,the total volumes of pancreatic islet was also increased by16.2%in the high-fat 2 group at 20^thh week.3.The level of fasting blood glucose was alike that of animals of type 2diabetes mellitus and remained stable in the diabetic model group.The level of fasting serum insulin and HOMA-IR of the diabetic model group was significantly increased by 55.0%and 43.8%respectively at 20^th week compared with that at 10^th week.Most of the pancreas islets were irregular in shape,the number of pancreatic isletβcell was significantly reduced and weak expression of insulin was present in the diabetic model group.A few of the pancreas islets were similar to that of the control group in the morphological structure in the diabetic model group.The total volumes of pancreatic islet and the ratio of immune positive areas in pancreatic islet of the diabetic model group were significantly reduced by 11.3%and 15.4%respectively at 20^th week compared with that at 10^th week.4.The level of fasting blood glucose of the non-diabetic model group was significantly increased by 28.1%at 20^th week compared with that at 10^thh week.There were 3,3,5,3 and 9 rats whose level of fasting blood glucose was larger than 7.8mmol/l in the non-diabetic model group at 12^th,14^th,16^th,18^th and 20^thh week.There were 2/7,6/10,8/10,18/27,15/24,22/26 and 16/20rats with impaired glucose tolerance respectively in the non-diabetic model group each week.Most of the pancreas islets were similar to that of the control group and a few were similar to that of the diabetic model group in the morphological structure in the non-diabetic model group.The total volumes of pancreatic islet and the ratio of immune positive areas in pancreatic islet of the non-diabetic model group were significantly lower than that of control group,but higher than that of the diabetic model group at 20^thh week.Conclusion:1.Long-term（20 weeks）high-fat diet led to insulin resistance and dysfunction of pancreatic isletβcell in rats,but the morphological change of pancreatic isletβcell didn’t become evident.The formation of type 2 diabetes may need a long process.The degree of insulin resistance was significantly reduced and the function of pancreatic isletβ-cell was improved by early dietary intervention.2.Continued（10 weeks）high-fat diet didn’t obviously have an effect on the functional impairment and the morphological change of pancreatic isletβcell in the diabetic model.But the functional impairment of pancreatic isletβcell was further aggravated in the non-diabetic model group.It is possible that high-fat diet has more important effect on the formation stage of diabetes than the diabetes status.3.The level of fasting blood glucose was associated with duration of high-fat diet.