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  • Title: [Effects of aging on the expressions of insulin receptor substrate-1, phosphate protein kinase B in rat liver and muscle].
    Author: Wang S, Meng ZM, Li XJ.
    Journal: Sichuan Da Xue Xue Bao Yi Xue Ban; 2009 May; 40(3):426-9. PubMed ID: 19626997.
    Abstract:
    OBJECTIVES: To investigate the effects of aging on the levels of free fatty acid (FFA), lipid profile, the expression of IRS-1 and its downstream signal Akt phosphorylation, so to explore the mechanisms of aging-associated glucose tolerance impairment. METHODS: Three different age groups (6, 12, 20-24 months) of SD rats were used. After being fasted for 12-14 h, the rats were anesthetized with sodium pentobarbital (30 mg/kg BW, i.p.), then the samples of blood, liver and muscle were collected. Blood samples were used for the detection of fasting blood glucose, lipid profile and FFA. The expressions of IRS-1 and p-Akt in liver and muscle were measured by immunohistochemical staining method. RESULTS: 1) The level of FFA in 20-24 months groups was significantly higher [(419.94 +/- 93.93) vs (256.22 +/- 73.93) mmol/L, P<0.05] than that of younger group (6 months); 2) IRS-1 was expressed in liver and muscle cell of all groups. The level of IRS-1 showed no significant change in both liver and muscle. 3) p-Akt expression in liver significantly decreased in old rat when comparing to younger counterparts [2911.06 +/- 268.13 vs 4683.72 +/- 582.29 (12 months) & 4903.06 +/- 688.44 (6 months), P<0.05], while no difference was found in muscle among three age groups. CONCLUSION: 1) FFA was the initial metabolic change in natural aging SD rat, which might play an important role in age-related insulin resistance. 2) There was no significant difference of IRS-1 expression among three rat age groups. 3) PI3K/Akt pathway in liver of old rat is a critical signal defect of insulin dysfunction with aging. Liver might be main component organ involved to age-related insulin resistance.
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