Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I

Endocrinology. 1993 Oct;133(4):1783-8. doi: 10.1210/endo.133.4.7691581.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Line
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Female
  • Glomerular Mesangium / metabolism*
  • Glomerular Mesangium / pathology
  • Glucose / pharmacology
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / metabolism*
  • Mice
  • Osmolar Concentration
  • Receptors, Somatomedin / metabolism

Substances

  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Receptors, Somatomedin
  • Insulin-Like Growth Factor I
  • Glucose