Regulation of insulin-like growth factor I receptors in diabetic mesangial cells.
Mesangial cells are thought to play a central role in the renal complications of diabetes mellitus. Insulin-like growth factor I (IGF-I) has been found to promote mesangial cell proliferation and regulate normal mesangial cell function in an autocrine and/or paracrine fashion. To gain further insight into the potential regulatory role IGF-I may play in mesangial cell function in diabetes, IGF-I receptors were analyzed in mesangial cells isolated from diabetic mice (db/db) and their control littermates (db/m). Mesangial cells isolated from db/db mice exhibited higher levels of IGF-I receptors compared to cells from db/m mice. Insulin receptors were not detectable in either cell type by binding analyses; however, immunoblot analysis revealed insulin receptor alpha-subunits in wheat germ agglutinin-Sepharose-purified membranes from db/db cells. Northern blot analysis further indicated a lack of detectable insulin receptor mRNA in db/m cells, whereas db/db cells expressed multiple insulin receptor mRNA transcripts. Both IGF-I and insulin receptor mRNA levels were increased in db/db cells grown in the presence of high glucose (28 mM), whereas the receptor protein levels remained relatively constant or increased, respectively. This increased expression of IGF-I and insulin receptors in diabetic mesangial cells may have an important role in the development of diabetic nephropathy.
Oemar
B S
BS
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06510.
Foellmer
H G
HG
Hodgdon-Anandant
L
L
Rosenzweig
S A
SA
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism*; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin