Effect Of Zinc On Insulin Sensitivety And Its Mechanisms In Rats Fed With High Fat Diet

ObjectiveTo investigate the effects of zinc on the insulin sensitivity and its mechanisms in SD rats fed with high fat diet,it can explore the connection of zinc with Diabetes and insulin resistance.MethodsTotally 68 healthy male Sprague-Dawley rats were randomly allocated to two groups:normal diet group(n=29)and high fat diet group(n=39).At the end of the 17th week,the rats of the two groups were randomly assigned to five groups based on HOMA-IR.,each group was administered with distilled water or zinc at dose of 5,10,15 or 30 mg/kg daily by zinc lavage for 7 weeks.There was no difference between normal diet groups and high fat diet groups with HOMA-IR.At the end of the 17th week,blood was collection from inner canthus.With the experiment of the last,all rats were deprived of food overnight,then killed by withdraw blood from femoral.Livers were quickly excised and immediately frozen in liquid nitrogen for liver glycogen,mRNA and western bolt test.Serum FPG,TC,TG,HDL-c,FFA levels were assayed enzymatically what were use the automatic bio-system biochemistry analyzer.FINS were determined by ELISA kit,glycogen kit to detect the content of hepatic glycogen,fully automatic glycosylated hemoglobin analyzer detected HbA1c,HOMA-IR,ISI,LDL were calculated.The mRNA expression for PEPCK,G-6-Pase,GCK in the hepatic was determined by RT-PCR.The phosphorylation level of Akt,GSK,FoxO1 was detected by Western blot.Then to explore the mechanism where zinc to remit the insulin sensitivity in rats what caused by the high-fat diet.ResultsThe general situation of rats:not until the 18th week,did the normal diet group and high fat diet group show the difference of body weight,then found that the high-fat diet group is higher.The effect of zinc on insulin sensitivity:there is no obvious difference on FPG,FINS,HOMA-IR and ISI among different groups of zinc on normal diet group,no matter before or after lavage.There is also no obvious difference among different dose of zinc lavage groups on FPG,but FINS and HOMA-IR is higher after zinc administration,and ISI is lower than before.FINS and HOMA-IR is lower on 10mg and 15mg zinc administration groups than others group on rats fed with high fat diet.Further more,15mg/d zinc lavage group has higher ISI level than others zinc level administration on high fat diet group.After zinc lavage for 7 weeks,there is no difference on HbAlc and hepatic glycogen between normal diet groups and high fat diet groups,compared with same zinc dosage group.Zinc has the effect of the rat lipid metabolism:there is no significant difference on TC,HDL-c and LDL-c,between before and after different dosage of zinc oral administration on rats fed with normal diet,and TG is higher only on 30mg/d zinc lavage group,others were the same as before.As for rats fed with high fat diet,TC on 10mg zinc administration group is the same,while others are higher after zinc supplementation than before;TG on 30mg/d zinc administration group is higher after zinc supplementation,but others have no such finding;there is also no significant difference on HDL-c before and after zinc supplementation on different zinc dosage;only Omg/d and 5mg/d zinc dosage groups show increased LDL-c.After zinc supplementation,FFA are higher on high fat diet are higher than normal diet rats among four dosage zinc administration groups,except 30mg/d oral zinc dosage.Effect of zinc on key enzymes of hepatic glucose metabolism:GCK mRNA level on normal control group is lower than high fat control group and high fat+15mg zinc supplementation group.While PEPCK mRNA and G-6-Pase mRNA level are the same among this three groups.Effect of zinc on PI3K-AKT signaling pathways on rats' hepatic:the phosphorylation level of AKT and GSK is higher on high fat+15mg group rats than normal control group and high fat control group on basic situation;the phosphorylation level of AKT Ser473,GSK3(3 Ser9,FoxO1 Ser256 is higher when zinc and insulin both supplied than zinc supplied only;and higher than insulin supplied only on AKT Ser473,GSK3P Ser9.ConclusionsHigh fat diet rats with 10mg or 15mg zinc administration everyday for 7 weeks can delay the FINS increase caused by high fat diet,improve insulin sensitivity and delay the development of insulin resistance to a certain extent.Zinc also have positive effect on lipid profile on rats fed with high fat diet,10mg and 15mg zinc administration everyday foe 7 weeks can delay the increasing of TC,LDL-c and decreasing of HDL-c,but 30mg zinc can increase the TG and decrease of HDL-c.15mg/Kg·bw zinc administration have no significant influence on hepatic glycogen,translation of glycogen metabolism enzyme including GCK,PEPCK,and G-6-Pase.Zinc increases hepatic phosphorylation of AKT Ser473,GSK3P Ser9,FoxO1 Ser256 may be the one mechanism of zinc on improving insulin resistance on rats feed with high fat diet.