title: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I.
abstract: 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.
authors.affiliation: Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
authors.forename: S J
authors.initials: SJ
authors.lastname: Elliot
authors.forename: L J
authors.initials: LJ
authors.lastname: Striker
authors.forename: M
authors.initials: M
authors.lastname: Hattori
authors.forename: C W
authors.initials: CW
authors.lastname: Yang
authors.forename: C J
authors.initials: CJ
authors.lastname: He
authors.forename: E P
authors.initials: EP
authors.lastname: Peten
authors.forename: G E
authors.initials: GE
authors.lastname: Striker
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D005947:Glucose