Diabetes, Vol 41, Issue 2 222-226, Copyright © 1992 by American Diabetes Association
Tissue-specific regulation of basic fibroblast growth factor mRNA levels by diabetes
CW Karpen, RG Spanheimer, AL Randolph and WL Lowe
Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City.
Because basic fibroblast growth factor (bFGF) is recognized as an
angiogenic factor and diabetes is characterized by multiple vascular
complications, including diabetic microangiopathy, we examined the
regulation of tissue bFGF mRNA levels by diabetes. Diabetes was induced in
male Sprague-Dawley rats by injection of 125 mg/kg body wt i.v.
streptozocin (STZ), with intensive insulin therapy initiated in half of the
diabetic rats. Rats were killed 96 h postinjection of STZ. Tissue bFGF and
insulinlike growth factor I (IGF-I) mRNA levels were measured
simultaneously with a solution hybridization-RNase protection assay. bFGF
mRNA levels increased from 1.7- to 2.7-fold in eye, heart, lung, and brain
from diabetic compared with buffer-injected control rats. In skeletal
muscle, bFGF mRNA levels decreased to 23% of control levels, whereas bFGF
mRNA levels were unchanged in kidneys from diabetic versus control rats.
Changes in tissue bFGF mRNA levels were partially reversed by insulin
treatment in all tissues. In contrast, IGF-I mRNA levels were significantly
decreased from 15 to 50% of control levels in all tissues studied except
those in brain, which decreased to only 85% of control levels. These data
demonstrate that bFGF mRNA levels are altered by diabetes in a
tissue-specific fashion and are consistent with the hypothesis that
increased production of bFGF may contribute to the development of diabetic
microangiopathy in some tissues.