Effects of age on elements of insulin-signaling pathway in central nervous system of rats.
Insulin resistance is known to play a pivotal role in type 2 diabetes. Senile individuals, besides being prone to insulin resistance and, consequently, to type 2 diabetes, manifest diseases of the central nervous system (CNS) that may be influenced by disturbances of insulin signaling in the brain, such as memory impairment, Parkinson disease, and Alzheimer disease. We investigated the expression and response to insulin of elements involved in the insulin-signaling pathway in the forebrain cortex and cerebellum of rats ages 1 d to 60 wk. The protein content of insulin receptors and SRC homology adaptor protein (SHC) did not change significantly along the time frame analyzed. However, insulin-induced tyrosine phosphorylation of the insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from d 1 to wk 60 of life in both types of tissues. Moreover, the expression of SH protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin signal transduction and regulation of the insulin signal, decreased significantly with age progression, in both the forebrain cortex and the cerebellum of rats. Thus, elements involved in the insulin-signaling pathway are regulated at the expression and/or functional level in the CNS, and this regulation may play a role in insulin resistance in the brain.
Fernandes
M L
ML
Department of Internal Medicine, State University of Campinas, SP, Brazil.
Saad
M J
MJ
Velloso
L A
LA
D048868:Adaptor Proteins, Signal Transducing; D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000032:analysis; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019000:Phosphotyrosine; D011972:Receptor, Insulin; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases