The Expressions Of PI3K,AKT1,AKT2and NFκB In The Liver Of Type2Diabetic Osteoporosis Rats

Objective: Osteoporosis and type2diabetes mellitus (T2DM) are nowprevalent in aging and westernized societies, and adversely affect the healthof the elderly people by causing fractures and vascular complications,respectively. Recent experimental and clinical studies show that bothdisorders are etiologically related to each other. Low bone mass is oftendetected in T1DM although the pathogenesis is likely to be multifactorial. Onthe other hand, BMD can be low, normal or increased in T2DM. Yet bothforms of diabetes are associated with an increased risk of fracture. Insulinresistance is a hallmark of type2diabetes mellitus. Impaired insulin signallingthrough the PI3K-AKT pathway is responsible for the impairment ininsulin-stimulated glucose metabolism type2diabetes patients. One area thathas received considerable attention has been the PI3K-AKT signaling pathway,which has emerged as a major survival network for osteoblasts. When the liverbecame insulin resistant, found an inccease in NFκB activity. At the same timeThe idea that osteoblasts, or their progenitors, support osteoclast formation byexpressing the activator of NFkB ligand (RANKL) is a widely held tenet.Themechanism of how T2DM influence osteoporosis is unclear and there is noreport about whether they have common pathogenesis. In this study, weestablished type2diabetes osteoporosis rat model, measured the hepatic geneexpression involved in insulin signaling pathway in Type2diabeticosteoporosis rats and discussed the relationchip of the pathogenesis of thesetwo diseases.Methods:100Wistar rats were randomly divided into four groups after1week feeding: normal control group(NS,N=24), ovariectomy group(NOVX,N=26), type2diabetes control group(DS,N=24), type2diabetic rats underovariectomy group (DOVX,N=24). The weight of rats in the four groups had no significant difference. The T2DM rats model was made by feeding themwith high-sugar-fat feedstuff and injected small doses of STZ, andovariectomied to make the osteoporosis rats model. At4,8,12weeks afterovariectomy, five rats was randomly executed, the liver of which wasseparated after anesthesia. The expression of PI3K,AKT1,AKT2,NFκB atprotein level was detected by IHS (immunohistochemistry) while theexpression of PI3K,AKT1,AKT2,NFκB at mRNA level was detected byRT-PCR. The experimental data was presented as mean±standard deviation.Variance Analysis were used to check differences between groups bySPSS13.0,P<0.05was considered statistically significant.Results:1The expression level of PI3K1.1Immunohistochemistry results: the expression of PI3K is located incytoplasm of the hepatocyte. At4weeks after ovariectomy, the expression ofPI3K in NOVX group is significantly higher than that in NS group(P<0.05), inDOVX group is significantly lower than that in DS group(P<0.05), in DS andDOVX group is significantly higher than that in NS and NOVXgroups(P<0.05); At8weeks after ovariectomy, the expression of PI3K inNOVX group is significantly lower than that in NS group(P<0.05), in DOVXgroup is significantly higher than that in DS group(P<0.05), in DS group issignificantly lower than that in NS group(P<0.05), in DOVX group issignificantly higher than that in NOVX group(P<0.05); At12weeks afterovariectomy, the expression of PI3K in NOVX group is significantly higherthan that in NS group(P<0.05), in DOVX group is significantly lower thanthat in DS group(P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05).1.2RT-PCR results: At4weeks after ovariectomy, the expression ofPI3K in NOVX group is significantly higher than that in NS group(P<0.05), inDOVX group is significantly lower than that in DS group(P<0.05), in DS andDOVX groups is significantly higher than that in NS and NOVX groups(P<0.05); At8weeks after ovariectomy, the expression of PI3K inNOVX group is significantly lower than that in NS group(P<0.05), in DOVXgroup is significantly higher than that in DS group(P<0.05), in DS group issignificantly lower than that in NS group(P<0.05), in DOVX group issignificantly higher than that in NOVX group(P<0.05); At12weeks afterovariectomy, the expression of PI3K in NOVX group is significantly higherthan that in NS group(P<0.05), in DOVX group is significantly lower than thatin DS group(P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05).2The expression level of AKT12.1Immunohistochemistry results: the expression of AKT1is located incytoplasm of the hepatocyte. At4weeks after ovariectomy, the expression ofAKT1in NOVX and DOVX groups is significantly lower than that in NS andDS groups(P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05)；at8weeks after ovariectomy, the expression of AKT1inNOVX group is significantly higher than that in NS, but there is no significantdifference between NOVX and DS groups(P>0.05), the expression of AKT1in DOVX and DS groups is lower than that in NOVX and NS groups；at12weeks after ovariectomy, the expression of AKT1in NOVX group issignificantly higher than that in NS group, in DOVX group is lower than thatin DS group(P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05).2.2RT-PCR results: At4weeks after ovariectomy, the expression ofAKT1in NOVX and DOVX groups is significantly lower than that in NS andDS groups (P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05); at8weeks after ovariectomy, the expression of AKT1inNOVX group is significantly higher than that in NS group(P<0.05), but there is no significant difference between NOVX and DS groups (P>0.05), theexpression of AKT1in DOVX and DS groups is lower than that in NOVX andNS groups; at12weeks after ovariectomy, the expression of AKT1in NOVXgroup is significantly higher than that in NS group, in DOVX group is lowerthan that in DS group(P<0.05), in DS group is significantly higher than that inNS group(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05);3The expression level of AKT23.1Immunohistochemistry results: the expression of AKT2is located incytoplasm of the hepatocyte. At4weeks after ovariectomy, the expression ofAKT2in NOVX group is significantly higher than that in NS group(P<0.05),in DOVX group is significantly lower than that in DS group(P<0.05), butthere is no significant difference between DS and NS groups (P>0.05), theexpression of AKT2in DOVX group is significantly lower than that in NSgroup(P<0.05); At8weeks after ovariectomy, there is no statistic differencesbetween NS and NOVX groups(P>0.05), there is no significant differencebetween between DOVX and DS groups (P>0.05), the expression of AKT2inDS and DOVX groups is significantly lower than that in NS and NOVXgroups(P<0.05); At12weeks after ovariectomy, the expression of AKT2inNOVX group is significantly higher than that in NS group(P<0.05), in DOVXgroup is significantly lower than that in DS group(P<0.05), in DS andDOVX groups is significantly lower than that in NS and NOVXgroups(P<0.05).3.2RT-PCR results: At4weeks after ovariectomy, the expression ofAKT2in NOVX group is significantly higher than that in NS group(P<0.05),in DOVX group is significantly lower than that in DS group(P<0.05), there isno significant difference between DS and NS groups(P>0.05), the expressionof AKT2in DOVX group is significantly lower than that in NSgroup(P<0.05); At8weeks after ovariectomy, there is no statistic differencesbetween NS group and NOVX groups(P>0.05), there is no significantdifference between between DOVX and DS groups (P>0.05), the expression of AKT2in DS and DOVX groups is significantly lower than that in NS andNOVX groups(P<0.05); At12weeks after ovariectomy, the expression ofAKT2in NOVX group is significantly higher than that in NS group(P<0.05), in DOVX group is significantly lower than that in DS group(P<0.05), in DS and DOVX groups is significantly lower than that in NS andNOVX groups(P<0.05).4The expression level of NFκB4.1Immunohistochemistry results: the expression of NfκB is located incytoplasm of the hepatocyte. At4weeks after ovariectomy, the expression ofNfκB in NOVX group is significantly higher than that in NS group(P<0.05),there is no significant difference between DOVX and DS groups(P>0.05), theexpression of NfκB in DS group is significantly higher than that in NSgroup(P<0.05) there is no significant difference between DOVX and NOVXgroups (P>0.05); At8weeks after ovariectomy, the expression of NFκB inNOVX group is significantly higher than that in NS group(P<0.05), in DOVXgroup is lower than that in DS group(P<0.05), in DS group is significantlylower than that in NS group(P<0.05), in DOVX group is significantly lowerthan that in NOVX group(P<0.05); At12weeks after ovariectomy, theexpression of NfκB in NOVX group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in DS group(P<0.05), in DS group is significantly higher than that in NS group(P<0.05), inDOVX group is significantly lower than that in NOVX group(P<0.05)..4.2RT-PCR results: At4weeks after ovariectomy, the expression ofNFκB in NOVX group is significantly higher than that in NS group(P<0.05),there is no significant difference between DOVX and DS groups(P>0.05), theexpression of NfκB in DS group is significantly higher than that in NSgroup(P<0.05), there is no significant difference between DOVX and NOVXgroups(P>0.05); At8weeks after ovariectomy, the expression of NfκB inNOVX group is significantly higher than that in NS group(P<0.05), in DOVXgroup is lower than that in DS group(P<0.05), in DS group is significantlylower than that in NS group(P<0.05), in DOVX group is significantly lower than that in NOVX group(P<0.05); At12weeks after ovariectomy, theexpression of NFκB in NOVX group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in DSgroup(P<0.05), in DS group is significantly higher than that in NSgroup(P<0.05), in DOVX group is significantly lower than that in NOVXgroup(P<0.05)..Conclusion:1The expression of PI3K,AKT1,AKT2and NFκB in the liver of NOVXgroup rats is higher than that of NS group rats as a whole.2The expression of PI3K,AKT1,AKT2and NFκB in the liver of DOVXgroup rats is lower than that of DS group rats in the early then it becomedecreased.3The expression of PI3K,AKT1,AKT2and NFκB in the liver of DOVXgroup rats is higher than that of DS group rats as a whole.4The expression of PI3K,AKT1,AKT2and NFκB in the liver of DOVXgroup rats is lower than that of NOVX group rats as a whole.5The inhibition of the expressions of PI3K,AKT1,AKT2and NFκB inthe liver of DOVX maybe related to the pathogenesis of Type2diabetes withosteroposis.