Des(1-3)IGF-1 treatment normalizes type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in predegenerative retina of diabetic rats.
Little is known about interventions that may prevent predegenerative changes in the diabetic retina. This study tested the hypothesis that immediate, systemic treatment with an insulin-like growth factor (IGF)-1 analog can prevent abnormal accumulations of type 1 IGF receptor, and phospho-Akt (Thr 308) immunoreactivity in predegenerative retinas of streptozotocin (STZ) diabetic rats. Type 1 IGF receptor immunoreactivity increased approximately 3-fold in both inner nuclear layer (INL) and ganglion cell layer (GCL) in retinas from STZ rats versus nondiabetic controls. Phospho-Akt (Thr 308) immunoreactivity increased 5-fold in GCL and 8-fold in INL of STZ rat retinas. In all cases, immunoreactive cells were significantly reduced in STZ des(1-3)IGF-1-treated versus STZ rats. Preliminary results suggested that vascular endothelial growth factor (VEGF) levels may also be reduced. Hyperglycemia/failure of weight gain in diabetic rats continued despite systemic des(1-3)IGF-1. These data show that an IGF-1 analog can prevent early retinal biochemical abnormalities implicated in the progression of diabetic retinopathy, despite ongoing hyperglycemia.
University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
A
A
Kummer
B E
BE
Pulford
D N
DN
Ishii
G M
GM
Seigel
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D010769:Phosphothreonine; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D017384:Sequence Deletion; D015431:Weight Loss / Q000187:drug effects
D011518:Proto-Oncogene Proteins; D010769:Phosphothreonine; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt