IGF-I mRNA and signaling in the diabetic retina
| Autor: | Giulio R. Romeo, Francesca Podesta, Mara Lorenzi, Chiara Gerhardinger, Kimberly D. McClure |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Aging Time Factors Endocrinology Diabetes and Metabolism Apoptosis Biology Protein Serine-Threonine Kinases Retina Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Diabetes mellitus Proto-Oncogene Proteins Internal Medicine medicine Cadaver Diabetes Mellitus Animals Humans RNA Messenger Insulin-Like Growth Factor I Phosphorylation Protein kinase B Aged Retinal Vessels Retinal Receptors Somatomedin Middle Aged medicine.disease Capillaries Rats medicine.anatomical_structure Endocrinology chemistry Growth Hormone sense organs Signal transduction Proto-Oncogene Proteins c-akt Retinopathy Signal Transduction |
| Zdroj: | Diabetes. 50(1) |
| ISSN: | 0012-1797 |
| Popis: | IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. Because in diabetes vascular and neural cells of the retina undergo accelerated apoptosis, we examined IGF-I synthesis and signaling in the human and rat diabetic retina. In retinas obtained postmortem from six donors aged 64 ± 8 years with a diabetes duration of 7 ± 5 years, IGF-I mRNA levels were threefold lower than in the retinas of six age-matched nondiabetic donors ( P = 0.005). In the retinas of rats with 2 months9 duration of streptozotocin-induced diabetes, IGF-I mRNA levels were similar to those of control rats, but after 5 months of diabetes they failed to increase to the levels recorded in age-matched controls ( P < 0.02). Retinal IGF-I expression was not altered by hypophysectomy, proving to be growth-hormone independent. IGF-IR levels were modestly increased in the human diabetic retinas ( P = 0.02 vs. nondiabetic retinas) and were unchanged in the diabetic rats. Phosphorylation of the IGF-IR could be measured only in the rat retina, and was not decreased in the diabetic rats (94 ± 18% of control values). In the same diabetic rats, phosphorylation of Akt was 123 ± 21% of control values. There was not yet evidence of increased apoptosis of retinal microvascular cells after 5 months of streptozotocin-induced diabetes. Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|