Effect of IGF-I on DNA, RNA, and protein loss associated with brain atrophy and impaired learning in diabetic rats.
Brain atrophy in diabetic dementia (DD) may be due to a catabolic state with DNA loss. Insulin-like growth factor (IGF) levels are reduced in diabetes, and IGF replacement may ameliorate brain protein loss. Subcutaneous minipumps released vehicle (Db + Veh) or IGF-I (Db + IGF-I) in diabetic rats. Brain wet, dry, and water weights as well as DNA, rRNA, poly(A)+ RNA, and protein contents per brain were significantly reduced in diabetic rats. In the remaining brain cells, there was a significant decline in ratios of (rRNA/DNA) and (protein/DNA). IGF-I administration partially prevented the loss of brain protein content independently of hyperglycemia (P < 0.03). This is the first demonstration of a severe disturbance in the brain protein regulatory pathway together with DNA loss in diabetes. Because Alzheimer's Disease (AD) is associated with a diabetes-like brain environment, a catabolic state may contribute to brain atrophy in sporadic AD as well as DD.
Lupien
Sean B
SB
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Bluhm
Erik J
EJ
Ishii
Douglas N
DN
D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004247:DNA / Q000187:drug effects*; D003704:Dementia / Q000517:prevention & control; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008297:Male; D011506:Proteins / Q000187:drug effects*; D012313:RNA / Q000187:drug effects*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D011506:Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I; D004247:DNA