Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I.
Experimental evidence has suggested that insulin-like growth factor-I (IGF-I) may contribute to diabetic complications. Previously, we and others have shown that normal glomerular mesangial cells have receptors for, synthesize, and exhibit a mitogenic response to IGF-I. We investigated the IGF-I response in cells derived from a genetic model of diabetes, the nonobese diabetic (NOD) mouse. Mesangial cell lines were derived from diabetic (D-NOD) and nondiabetic adult mice. D-NOD cells released more IGF-I into the supernatant and had a decreased binding of IGF-I to surface receptors. Analysis according to Scatchard revealed a decreased number of receptor sites on D-NOD cells, although the structure of the IGF-I receptor visualized by cross-linking was identical for both cell types. Preincubation of D-NOD cells with an antibody to IGF-I resulted in an increase in the number of receptor sites. This suggested that autocrine IGF-I was responsible for the decrease in D-NOD receptor number and that diabetes had resulted in a stable phenotypic change.
Elliot
S J
SJ
Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Striker
L J
LJ
Hattori
M
M
Yang
C W
CW
He
C J
CJ
Peten
E P
EP
Striker
G E
GE
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009994:Osmolar Concentration; D017451:Receptors, Somatomedin / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D005947:Glucose