[Effects of aging on the expressions of insulin receptor substrate-1, phosphate protein kinase B in rat liver and muscle].
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Shuang
S
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.
Meng
Zhang-min
ZM
Li
Xiu-jun
XJ
D000375:Aging; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005230:Fatty Acids, Nonesterified; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt