| ObjectiveInvestigating the morphology and function of pancreatic fatty infiltration in different degree on pancreatic islets of diet-induced obesity Sprague-Dawley rats.MethodsSeventy weanling SD male rats were randomly divided into two group:the normal chow group (N group, w=10) and the high-fat diet group (F group, n=60). Thirty-four diet-induced obesity rat models were established successfully by feeding a normal diet or a fat-enriched diet for each group after 18 weeks. The obese male rats were divided into three groups according to their weight:the mild-obesity group (A group, n=11), the moderate-obesity group (B group, n=11) and the severe-obesity group(C group,n=12). Then the body weight was measured and the Lee’s index calculated.And fasting plasma insulin(FINS),Free Fatty Acid(FFA),Interleukin-6(IL-6) and Tumor Necrosis Factor alpha(TNF-a) were determined after fasting blood drawing. After an oral glucose tolerance test(OGTT), the insulin secretory function of the islet was evaluated by HOMA-IR, HOMA-β, △I30/△G30 and area under curve of insulin(0-120min) afer drawing blood of different point in time to detect blood glucose and insulin. Pancreatic Triglyceride(TG) was measured after pancreatic tissue separation. Histological changes of Pancreatic fatty filtration were observed with the light microscope after pancreatic H.E. Staining, and morphological analysis of the pancreatic islet was assessed by immunohistochemistry.Results.The Lee’s index was significantly higher than the corresponding control group(A group vs N group, B group vs A group, C group vs B group) [(324.92±8.17) vs (308.15±5.93), (328.33±9.0) vs (324.92±8.17), (329.95±4.68) vs (328.33±9.02), P < 0.01]. Compared with N group,fasting plasma FFA was significantly higher in A, B and C group[(324.92±8.17)umol/Lvs (399.26±22.41)umol/L,(328.33±9.02)umol/L vs (399.26±22.41)umol/L,(329.95±4.68)umol/L vs (399.26±22.41)umol/L, P< 0.01]. Fasting plasma FFA was significantly higher in C group than that in A and B group. [(499.85±37.17)umol/L vs (457.58±31.28)umol/L,P< 0.01 and (499.85±37.17) umol/L vs (465.88±26.16)umol/L, P< 0.05]. Compared with N group, pancreatic TG was significantly higher in C group [(324.52±55.82)umol/L vs (269.57±50.45) umol/L, (778.14±143.55)umol/L vs (437.60±136.08)umol/L, P< 0.05].2.As to OGTT, the serum glucose levels in 30min and 60min were significantly higher in A, B and C group [(9.71±0.88)mmol/L vs (8.47±0.34)mmol/L, (9.93±0.64)mmol/L vs (8.47±0.34)mmol/L, (10.48±0.71)mmol/L vs (8.47±0.34) mmol/L, (8.26±0.77)mmol/L vs (6.60±0.59)mmol/L, (9.38±0.45)mmol/L vs (6.60±0.59)mmol/L, (10.62±0.61)mmol/L vs (6.60±0.59)mmol/L, P< 0.01]and the serum glucose levels in 120min were also significantly higher in Brand C group [(5.47±0.32)mmol/L vs (5.10±0.41)mmol/L, (5.66±0.20)mmol/L vs (5.10±0.41) mmol/L, P< 0.05]. As to B group, the insulin was significantly increased at 0 min and 60 min [(11.19 ±1.27)mIU/L vs (9.82±1.07)mIU/L, P< 0.05. (68.29 ±10.09)mIU/L vs (50.79±7.03)mIU/L, P< 0.01]. As to C group, the insulin was significantly increased at 60 min[(61.18±10.78) mlU/L vs (50.79±7.03)mIU/L, P< 0. 05].3.Compared with N group, HOMA-IR was significantly higher in B group [(2.27±0.31) vs (1.91±0.26), P< 0.01]. I30/△G30 was significantly lower in B and C group [(8.90 ±2.23) vs(12.56±3.38), P< 0.05. (7.41 ±2.00) vs (12.56±3.38), P< 0. 01]. The area under the curve of insulin (0-120min) was significantly increased in B group[(5867.41±476.27) vs (4976.90±654.93), P< 0.01].4.Plasma IL-6 level was significantly higher in A, B and C group [(4.94±0.62)pg/ml vs (3.91±1.15)pg/ml, (5.50±1.09)pg/ml vs (3.91±1.15)pg/ml, (7.84±3.46)pg/ml vs (3.91±1.15)pg/ml, P< 0.05]and Plasma TNF-a level was significantly higher in B and C group[(10.77±0.80)pg/ml vs (9.80±0.92)pg/ml, (11.34±1.11)pg/ml vs (9.80±0.92)pg/ml, P< 0.05].5.There was an increased tend of pancreatic fatty filtration when observed with the light microscope after pancreatic H.E. Staining.6.1mmunohistochemistry showed that, as to A and B group, total pancreatic islet area became significantly larger[(928945±115739)A/um2 vs (694596±86573) A/um2, (1053418±126378)A/um2 vs (694596±86573)A/um2, P< 0.05]. As to C group, total pancreatic islet area became significantly lower[(40.28±4.15)% vs (52.28±5.86)%, P < 0.05], while the grey level was significantly increased[(156±29) vs (121±17), P< 0.01].ConclusionLong-term high-fat diet may reduce different degree of obesity and pancreatic fatty filtration and obesity level is consistent with the degree of pancreatic fatty filtration. Mild-moderate pancreatic fatty filtration leads to the delay of insulin secretion in early phase and insulin resistance, while the severe one causes the damage of inslet β-cell. It may be related with the activation of the inflammation interfereing in insulin signaling pathway by pancreatic fatty filtration. Severe pancreatic fatty infiltration may be a warning sign predicting early phase of type 2 diabetes as one of the risk factors of type 2 diabetes. |
