| Insulin resistance(IR) is said to be present when there is less than a normal biological response in liver ,fat and muscle for a given concentration of insulin.The morbidity of IR tends to increase with aging. Clinical states of ER such as obesity and type 2 diabetes mellitus are characterized by a number of additional abnormalities besides disturbance of glucose homeostasis, such as hypertension, dyslipidaemia and hypercoagulability, all of which are associated with an increased cardiovascular risk. The clustering of these metabolic risk factors has been termed 'insulin resistance syndrome' or 'metabolic syndrome' or 'syndrome X'. The mechanism of decreased insulin sensitivity in the aged population is still unclear. Along with the identification of PPAR ligands and the extensive research of its function, it has become a worldwide focus to explore the relation between IR and PPARy. There are some changes of gene expression during ageing. So we speculate that the changes of PPARy expression or activity perhaps contribute to the occurance of IR.To evaluate the insulin sensitivity of rats precisely, we adopted the MMT based on frequently sampled FVGTT.The insulin sensitivity index(SI) of young and aged rats was caculated with the software programmed by Sun Yat-sen University of Medical Sciences . The SI of the aged rats is statistically lower than the young group.It implied there exits IR for the aged rats.The expression of PPAR mRNA or protein or both is abundant in adipose tissue.It plays key role in adipogenesis. In this study we determinated the expression of PPAR at mRNA and protein level in adipose tissue by RT-PCR and wetern blot and compared the difference between the young and aged rats.The results show that the expression of PPAR at both level in aged group dramaticallydecreased.The expression of its response genes LPL and aP2 mRNA decreased either,but only the former reaches statistical difference. No detectable changes was found in both group of the expression of GLUT-4 mRNA. HSL is a rate limited enzyme of lypolysis in adipocyte.The level of HSL mRNA is significant lower in the aged group than the young group.Although expression of PPAR is low in muscle (less than 10% of that in adipose tissue),given that its central role in glucose disposal and peripheral insulin resistance,we examined the expression of PPAR mRNA and its target gene GLUT-4 mRNA in muscle of young and aged rats and found expression of both genes significantly decreased in aged group.In order to extending our results from animal to human,we then investigated the difference expression of PPAR mRNA in OM adipose from young and aged people by RT-PCR. We observed significant reduction of PPARYmRNA level in aged group. Simultaneously the extent of IR in aged group was more severed than young group.In one word,this study showed decreased expression of PPAR in OM adipose and muscle from aged rats, and decreased expression of PPAR in OM adipose from aged people.As a key transcription factor of adipo genesis, the changes of PPAR expression may contribute to the development of IR during ageing by blocking the differientiation of preadipocyte and damaging the function of mature fat cell. We can't conclude whether the reduction of PPAR expression with ageing contribute to insulin sensitizer just as PPARy + / - ) mice do.At least the decreased expression of PPAR perhaps serve as a protection by limiting progressive accumulation of adipose with ageing.
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