Effects Of Insulin And Exercise On The Function And Morphology Of Pancreatic Islet Cell In High-fat Fed Rat

ObjectiveThe aim of the study is to observe the effects of insulin and swimming on the function and morphology of pancreatic islet cell in High-fat diet rats, and to investigate the relationship between the improvement of insulin sensitivity and the protection of pancreatic islet function.MethodsNormal male Wistar rats(8 weeks old) were divided into two groups taking either normal chow(NC, n=15), or high-caloric and high-fat diet(HF, n=60). Sixteen weeks later, 45 HF rats were treated with insulin(Lantus,4IU /kg, IN, n=15), swimming(SW, n=15), or insulin & swimming(I+S, n=15) for 8 weeks respectively. Insulin resistance was assessed by euglycemic hyperinsulinemic clamp technique. Insulin secretion of islet was evaluated by intravenous insulin releasing test. Morphological and quantitative analysis was performing on pancreatic tissues stained by double-label insulin and glucagon immunohistochemistry. Proinsulin mRNA was detected by RT-PCR. Blood glucose, triglyceride and free fatty acids(FFA) were measured by corresponding oxidase.ResultsHigh-fat fed rats had severe visceral obesity and developed remarkable insulin resistance compared with normal-chow rats, whereas the insulin sensitivity in SW and I+S rats had been significantly improved. Immunohistochemistry showed HF rats had a larger islet size (P<0.01) and significantly reduced insulin relative concentration ofβcells, as compare with NC rats(P<0.01). The islet relativeβcell volume was decreased significantly (P<0.01), whereas the relativeαcell volume increased (p<0.01). So the ratio ofβtoαcells were lower in HF(P<0.05). As compared with HF rats, SW rats had a higher insulin relative concentration ofβcells(P<0.01)and lower islet size(P<0.05). Swimming intervention resulted in a significant increase in the islet relativeβcell volume(P<0.01), and so was the ratio ofβtoαcells(P<0.05). The peak of insulin secretion in IVIRT in NC and SW was on 5min, whereas that in HF rats was on 10min. AUC(area under curve)10~60 of insulin in HF was higher than NC and SW rats(P<0.05). As compared with HF rats, insulin intervention resulted in slight increase in the islet relativeβcell volume(P<0.05), but had no change on the ratio ofβtoαcells. The peak of insulin secretion in IVIRT in NC and IN was on 5min, whereas that in HF rats was on 10min. AUC(area under curve)10~60 of insulin was comparable in HF and IN rats. With the improvement of insulin sensitivity, I+S rats had an increased islet relativeβcell volume and the ratio ofβtoαcells, so was the insulin relative concentration ofβcells. All the parameters was comparable between I+S and SW rats. Proinsulin mRNA level had no significant difference among 5 groups.ConclusionLong-term high-caloric and high-fat diet results in early impairment of islet morphology and function, and significant insulin resistance as well. It shows in the early course of Type 2 diabetes mellitus the adaptation of islet has already been impaired. By meliorating insulin resistance, exercise can reverse the early change of morphology and function of pancreatic islet. Insulin intervention may partly restore the secretion of pancreatic beta cell but cannot gain effective protection of pancreatic islet as swimming group without the improvement of insulin sensitivity. These findings demonstrate that when the functional defect of pancreatic islet is apparent early in the natural history of diabetes with the development of insulin resistance, improving insulin resistance will be more important and effective method than giving extraneous insulin to retain the morphology and function of pancreatic islet.