| Objective:To explore the value of 3.0 T magnetic resonance and IDEAL-IQ sequence detect the fat content of pancreas on type 2 diabetes BAMA mini pig,and explore the effect of pancreatic fatty infiltration in the development of type 2 diabetes and other influence of insulin secretion and glucolipid metabolism.Materials and methods:1.Thirteen pigs were divided into the experimental group(7 pigs)and the control group(6 pigs),used the random number table method.Normal diet was used for fed those pigs until the end of 5th month,and then,from the 6th month,the experimental group was fed with high-fat high-sugar,and then repeatedly injected small doses of Streptozotocin(STZ)through the ear vein.The type 2diabetes was considered successful when the fasting blood glucose was greater than 7.0mmol/L and the OGTT showed that the glucose tolerance was impaired.Meanwhile,the control group continued to fed with normal diet.Every month,a diabetic pig and a normal pig was randomly selected for MRI scan,fresh pancreatic specimens were obtained after each scan,we measured the pancreatic fat content(PFC)through acid hydrolysis,at the same time,some specimens were taken for pathological examination.The proton density fat fraction(PDFF)of the pancreas was measured in the fat mapping of the IDEAL-IQ sequence.In the head,the body and the tail region of the pancreas,the ROI was manually traced.The consistency of the two measurements was assessed used the Bland Altman method,and the correlation coefficient(ICC)in the group was used to described the differences between the participants,spearman correlation analysis was used to explored the correlation between pancreatic PDFF and the fat content of fresh pancreatic specimen.The linear regression equation was used to obtain the slope and intercept of the fitting line,for predicting the actual fat content of fresh pancreas.2.The weight,fast Blood glucose(GLU),insulin(INS),cholesterol total(TCHO),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL)and homocysteine(HCY)of BAMA mini pigs were measured in the morning of MRI scan,meanwhile the Insulin sensitivity index(ISI),Homeostasis model assessment insulin resistance(HOMA-IR),HOMA-βand Insulin action index(IAI)were calculated.3.Statistical analysis was performed by SPSS22.0 software,Kolmogorov-Smirnov method was used to tested whether the samples conformed with the normal distribution,used independent samples t test(normal distribution)or Mann-Whitney U test(non normal distribution)judged the difference of weight,pancreatic fat content,blood glucose,blood lipid,insulin and other biochemical indicators,between experimental group and control group.The one-way analysis of variance(One-way ANOVA)was used to compared the fat distribution in Bama miniature pig’s pancreatic head,body and tail,used the Pearson(for normal distribution)or Spearman(unsatisfied with the normal distribution)analysis of the correlation between pancreatic fat fraction(PFF)and fresh specimens of pancreatic fat content(PFC)with the method of acid hydrolysis of the pancreatic tissue and the weight,blood glucose,lipids,insulin and other biochemical indicators.The regression equation was verified by the linear regression equation analysis of the pancreatic fat fraction(PFC)and the pancreatic fat content(PFF)and weight.The difference of P<0.05 was statistically significant.Results:1.At the time of fifth month with normal feeding,there were no significant difference in weight,fasting blood glucose,fasting insulin and other indexes between the experimental group and the control group,weight(kg)was 28.50±2.35 and 27.20±3.49(t=-0.776,p=0.456),GLU(mmol/L)was 4.83±0.43 and5.17±0.33(t=-1.551,p=0.149),INS(mU/L)was 27.56±5.93 and 28.73±2.25(t=-0.456,p=0.657),TCHO(mmol/L)was 5.03±0.91 and 4.62±0.83(t=-0.876,p=0.476),TG(mmol/L)was 0.79±0.41 and 0.71±0.09(t=-0.416,p=0.687),HDL(mmol/L)was1.43±0.34 and 1.42±0.35(t=0.390,p=0.969),LDL(mmol/L)was 1.79±0.37 and 1.75±0.32(t=0.182,p=0.860),HCY(μmol/L)was 7.06±1.95 and 6.95±2.12(t=-0.098,p=0.924),respectively.As the feeding time was prolonged,the weight,GUL,TG,TCHO,and LDL,HOMA-IR of the experimental group showed a significant upward trend.While INS,HDL and HOMA-βshowed a trend of decrease,and had the significantly different from the control group.HCY was no significant difference between experimental group and control group.When the end of experiment,there were significant difference between experimental group and control group,weight(kg)was 88.99±11.85 and 58.67±9.22(P<0.001),GLU(mmol/L)was 18.06±6.03 and 5.06±1.41P<0.001),INS(mU/L)was 21.59±2.93 and 29.32±3.27,TCHO(mmol/L)was 4.36±1.14 and 2.98±0.56(P=0.021),TG(mmol/L)was 3.63±1.64 and 0.89±0.38(P=0.002),HDL(mmol/L)was1.24±0.20 and1.69±0.29(P=0.007),LDL(mmol/L)was 2.66(1.92~3.72)and 1.78(1.39~2.80)(P=0.015),HOMA-IR was 16.83±4.22、6.70±2.45(P<0.001),HOMA-βwas 1.50±0.24 and 2.77±0.45(P<0.001),IAI was-2.57±0.11、-2.15±0.15(P<0.001),respectively.2.The pathological results of pancreatic tissue showed that the fat content of pancreas in group T2DM was significantly increased,especially,the fat content in the central region of the pancreas of T2DM group was significantly higher than the control group.The pancreatic fat content included two parts of interstitial fatty infiltration and parenchyma fatty degeneration,fat distribution in the pancreas was extremely uneven,fatty infiltration was a wedge-shaped,it was from peripheral regions to the central regions,gradually.The degree of the fatty infiltration in peripheral regions was significantly higher than that of the central regions.3.There was no significant difference of PFF between the head,body and tail which were measured by MRI.There was no significant difference in PFF between the two surveyors(t=-0.477,P=0.642).The intra group correlation coefficient(ICC)of the two measurements was 0.954(95%confidence interval was 0.848 to 0.986,P<0.001).The PFF value of the pancreas measured by the two surveyors was highly consistent with the Bland Altman method.4.There were positive correlation between PFF and PFC,weight,TG,TCHO and LDL,the correlation coefficients were 0.928,0.919,0.824,0.828,0.824(P<0.001),respectively.The moderate positive correlation were founded between PFF and GLU,HOMA-IR,correlation coefficients were 0.659(P=0.014),0.611(P=0.027),respectively.The moderate negative correlation were founded between PFF and HDL,INS,HOMA-βand IAI,the correlation coefficients were-0.594(P=0.032),-6.17(P=0.025),-0.607(P=0.028),-0.603(P=0.029),respectively.There was no correlation between PFF and feeding time(Age)and HCY,the correlation coefficients was 0.385(P=0.194),0.236(P=0.437),respectively.5.The regression equation was established:Y=0.69x+9.76,Y representative pancreatic fat content(PFC),the x representative pancreatic fat fraction(PFF)which was directly measured by MRI,the number of 9.76 is constant,through statistical tests,the regression equation was statistically significant(F=67.82.P<0.001),and the linear regression equation with a good fitting degree(R~2=0.86).Conclusion:1.This study confirmed that the T2DM model of Bama miniature pigs can be obtained through multiple injection of STZ with low-dose and feeding of fodder with high fat and high glucose.It can be used in related basic research.2.The pancreas fat content of T2DM Bama miniature pigs is significantly higher than that of the control group,and the pancreatic fat content in the T2DM model are composed of two parts of fat infiltration in the pancreatic interstitium and fat degeneration in the pancreas,and the fat distribution in the pancreas is uneven extraordinary.3.This study confirms that the IDEAL-IQ sequence of MRI can be used to measure the fat content of pancreas accurately,it is providing a reference for early diagnosis,prognosis and therapeutic evaluation of pancreatic pathological changes in T2DM patients.4.The weight,triglyceride,total cholesterol,fasting blood glucose and insulin resistance index were independent risk factors for pancreatic fat infiltration.High density lipoprotein,fasting insulin,HOMA-βand insulin activity index were protective factors of pancreatic fat infiltration.5.This study suggests that the relationship between the pancreas fat content and the metabolism of blood glucose and lipid are mutual influence.Monitoring pancreatic fat content by MRI can provide basis of reference and evaluation for the selection of new therapeutic targets and long-term prognosis of lipid-lowering treatment in clinic. |
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