Age-related changes in abundance of insulin/insulin-like growth factor-I hybrid receptors in rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 780-806-Determinants of Insulin Resistance & Associated Metabolic Disturbances
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-803
Mayumi Ishikawa*1, Toshisuke Morita2, Shiro Minami3 and Gen Yoshino2
1Nippon Medical School, Musashikosugi Hospital, Kawasaki, Japan, 2Toho University School of Medicine, 3Nippon Medical School, Kanagawa, Japan
Insulin/insulin-like growth factor-I (IGF-I) hybrid receptors (HRs) have been known as the affinity against insulin is lower than that of insulin/insulin receptor.  However, the physiological roles of HRs are not clear.  In the present study, we have investigated the effects of aging and GH-IGF-I system on the expression of HRs in rats, and addition, the expressions of HRs were observed in relation to glucose metabolism.

Muscle, liver, thigh fat and blood were collected from 2 weeks, 4 weeks, 4 months and 1 year-old male SD rats or spontaneous dwarf rats (SDRs), which have GH deficiency.  The 2 week-old rats were separated from their mother 1 hour before sacrifice, and the others were sacrificed after overnight fasting.  The tissue lysates were immunoprecipitated using an anti-insulin receptor antibody.  The protein samples were electrophoresed by SDS-page, and membranes were probed with anti-IGF-I receptor antibody, and the amount of HR was determined.  The tissue lysate after immunoprecipitation, which had insulin receptor removed, was immunoprecipitated again with anti-IGF-I receptor antibody, and the protein samples were electrophoresed, and probed with anti-IGF-I receptor antibody to investigate IGF-I/IGF-I receptor. HR and insulin/insulin receptor were investigated using the opposite method as above.  The serum concentration of glucose and insulin were measured and HOMA-R was calculated.

HR was 1.2 to 2.2-fold increased in each organ sample with aging. The insulin/insulin receptor and IGF-I/IGF-I receptor was decreased in each organ with aging.  The insulin/insulin receptor in each organ from 1-year old SD rat was about 0.2-fold compared to 2 week-old SD rat.  There was significant correlation between serum concentration of insulin or HOMA-R and amount of HR in liver and fat.  There was no difference in amount of HR, insulin/insulin receptor and IGF-I/IGF-I receptor between SD rats and SDR.

 Our study clearly describes that the expression of HR increased, whereas  insulin/insulin receptor and IGF-I/IGF-I receptor decreased with aging.   The expression of HR was not influenced by the GH-IGF-I system.  It is shown that the fasting serum insulin levels are increased compensatory to decreased expression of insulin/insulin receptors and increased expression of HRs in the muscle, fat and liver of aging rats.

Nothing to Disclose: MI, TM, SM, GY

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