| Objective:The aim of this current study is to establish a diabetic rat model induced byhigh-fat and high-sugar diet combined with low-dose STZ injection, and to explorethe protective effect of dipeptidyl peptidase-4(DPP4) inhibitor, sitagliptin, on the βcells of rat pancreatic. The effect of its intervention to expression of peroxisomeproliferator-activated receptor-γ/Activator protein-1/Pancreatic derived factor (PPARγ/AP-1/PANDER) is also evaluated.Method：Male SD rats were randomly divided into two groups, one group was fed withhigh-fat and high-sugar diet, another group was fed with normal diet, and set it asnormal control group(NC group). After feeding10week, the rats fed by high-fat andhigh sugar were intraperitoneally administered of a small dose of STZ. And1weeklater, we measured the fasting blood glucose (FBG) from rat tails. Those ratswhose FBG were more than16.7mmol/L indicated successful diabetic rat model.These rats were divided into three subgroups, the sitagliptin-treated group(SITgroup), pioglitazone-treated group (PIO group, positive control group) and diabeticcontrol group (DM group, negative control group). Regular measured the fastingblood glucose and body weight of the rats at0W,4W,8W,12W,16W,20W duringthe experiment time. After20week, we drawn the abdominal aortic blood andseparated the pancreatic tissue to determine the lever of fasting serum insulin andfetuin-A by ELISA. RT-PCR and Western blot were used to detected the expressionlevels of PPARγ, AP-1, PANDER in pancreatic. Results:After observed for20week, we found that:(1)The levels of blood glucosewas significantly decreased in the SIT group and PIO group after intervention(P＜0.05). Among these groups, the levels of blood glucose in SIT group and PIO groupdecreased than those of DM group (P＜0.05); and there was no significant differencebetween the SIT group and PIO group (P＞0.05).(2)The body weight of NC组wasrised than those before intervention(P＜0.05), and was decreased in DM group thanthose before intervention (P＜0.05), while there were no significant changes in theSIT group and PIO group (P＞0.05). Among these groups, The body weight of SITgroup and PIO group was significantly less than those of NC group (P＜0.05), butwas higher than those of DM group (P＜0.05); and there was no significantdifference between the SIT group and PIO group (P＞0.05).(3) The levels of serumfasting insulin in the SIT group and PIO group was significantly increased comparedto the DM group (P＜0.05); and there was no significant difference for SIT group tocompared to the PIO group and NC group (P＞0.05). The HOMA-β index of SITgroup and PIO group was significantly increased than those of DM group (P＜0.05);but it showed no significant difference for SIT group compared to PIO group (P＞0.05）.There was no significant difference in HOMA-IR index for SIT group tocompared to each groups (P＞0.05).(4)The levels of serum fetuin-A in SIT groupand PIO group was significantly lower than those of DM group (P＜0.05); and therewas no significant difference between the SIT group and PIO group (P＞0.05).(5)Compared to the DM group, the PPARγ expression in pancreas of SIT group wassignificantly increased (P＜0.05)，but the expression of AP-1, PANDER wasdecreased (P＜0.05); while compared to the PIO group, there was no significantdifference in the expression of PPARγ (P＞0.05), but the AP-1, PANDER expressionwas decreased (P＜0.05).Conclusion:(1) Sitagliptin can effectively control the levels of blood glucose in diabetic rats, buthave no significant effect on body weight.(2) Sitagliptin can increase levels of serum fasting insulin in diabetic rats and improve the function of pancreas β-cell.(3) Sitagliptin reduced the levels of serum fetuin-A in diabetic rats.(4) Sitagliptin can activate PPARγ, reducing the expression of AP-1/PANDER inpancreas, thereby protecting pancreatic β-cell. |
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