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.