关键词: 大鼠，Wistar , 营养性肥胖, 蛋白质, 胰岛素, 免疫组织化学, 胰高血糖素样肽 1

Abstract:

To investigate the effects of a longterm isocaloric highprotein diet on morphology and function of the pancreatic islet in dietinduced obese rats. Methods： Dietinduced obese rat models were established by feeding a fatenriched diet. The obese male rats were randomly divided into three groups: the highprotein diet group (HP group, n=12), the highfat diet group (HF group, n=11), and the normal food group (NC group, n=11). The total calorie ingestion of each rat per day was similar and was maintained for 24 weeks. Then body weight, visceral fat mass and fasting plasma glucagonlike peptide1 (GLP1) were determined. The insulin secretory function of the islet was evaluated by an intravenous glucose tolerance test (IVGTT), and morphological analysis of the  pancreatic islet was assessed by immunohistochemistry. ResultsCompared with the NC group, body weight ［(490.92±39.47)g vs (545.55±31.08)g, P＜0.01］ and visceral fat mass ［(22.42±7.04)g vs (32.33±9.27)g, P＜0.05］ in HP rats were significantly lower, but those indices were both higher ［(656.01±58.49)g  vs （545.55±31.08）g， （55.33±17.81）g vs（32.33±9.27）g， and both P＜0.01］ in the HF group. As to IVGTT, there were no differences in blood glucose among the three groups, but the serum insulin levels at 5min and 10 min were significantly lower in HP than in NC ［(91.56±21.72) mIU/L vs (121.29±34.03) mIU/L; (58.62±15.80) mIU/L vs (81.12±24.36) mIU/L, both P＜0.05］, and 0 min and 10 min insulin levels were significantly higher in HF than in NC［(40.21±14.12) mIU/L vs (27.48±11.31) mIU/L，(98.15±27.58) mIU/L vs (81.12±24.36) mIU/L, both P＜0.05］.  Plasma GLP1 level  was significantly lower in HP rats ［（0.52±0.13）μg/L vs（0.71±0.19）μg/L，P＜0.05］, and there was an  increased trend in the HF group ［（1.03±0.28）μg/L vs（0.71±0.19）μg/L, P=0.11］ compared with the NC group. Immunohistochemistry showed that there were no differences in morphology between HP and NC rats, but HF rats had a larger islet size，a lower ratio of insulin positive area to the islet，and a higher grey level（all P＜0.05）compared with NC rats. ConclusionCompared with impairment of islet morphology and function by highfat diets，longterm isocaloric highprotein intake may reduce the first phase secretion of insulin in dietinduced obese rats， but there was no alteration in islet morphology. The decrease of insulin secretion may be related to GLP1 decline and weight loss.

Key words: Dietinduced obesity; Protein; Insulin; Immunohistoc hemistry;  Glucagonlike peptide1； Rats, Wista