Insulin and IGF-I prevent brain atrophy and DNA loss in diabetes.
The aim of this study was to identify factors that regulate the bulk of adult brain mass, and test the hypothesis that concomitantly reduced insulin and insulin-like growth factor (IGF) levels are pathogenic for brain atrophy associated with impaired learning and memory in diabetes. Doses of insulin, or insulin plus IGF-I that were too small to prevent hyperglycemia were infused for 12 weeks into the brain lateral ventricles of streptozotocin-diabetic adult rats. Brain wet, water and dry weights were significantly decreased in diabetic rats; insulin prevented these decreases. The decrease in brain DNA and protein contents in diabetic rats was prevented by the combination treatment, but not by insulin alone. Levels of several glia- and neuron-associated proteins were reduced in diabetes; these reductions were also prevented by the combination treatment. Although hyperglycemia was not prevented in plasma or cerebrospinal fluid, insulin prevented brain atrophy but not bulk DNA loss in diabetes, whereas the combination prevented both. Insulin actively prevented the loss of brain water content as well. Brain atrophy is associated with concomitantly reduced levels of insulin and IGF in other disorders such as Alzheimer's disease.
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Predrag
P
Serbedzija
James E
JE
Madl
Douglas N
DN
Ishii
D000818:Animals; D001284:Atrophy / Q000503:physiopathology / Q000517:prevention & control; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000473:pathology*; D004247:DNA / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D048909:Diabetes Complications / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D007276:Injections, Intraventricular; D007328:Insulin / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D004338:Drug Combinations; D007328:Insulin; D009419:Nerve Tissue Proteins; D007334:Insulin-Like Growth Factor I; D004247:DNA