Receptors for and effects of insulin and IGF-I in rat glomerular mesangial cells.
Receptors for and biological effects of insulin and insulin-like growth factor I (IGF-I) were studied in cultured rat renal mesangial cells. Specific binding of 125I-IGF was over 200-fold greater (5.8%/0.2 mg cell protein) than the specific binding of 125I-insulin (0.2%/2 mg cell protein). Fifty percent inhibition of 125I-insulin binding was obtained with 8 x 10(-9) M unlabeled insulin. For 125I-IGF-I, 50% inhibition required 1.8 x 10(-9) M unlabeled IGF-I. 125I-IGF-I was also displaced by IGF-II and insulin but at 10-and 100-fold lower potencies, respectively, than IGF-I. Cross-linking of 125I-insulin and 125I-IGF-I to their receptors, using disuccinimidyl suberate (DSS), and identification of the receptor with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed a band with a molecular mass of 135 kDa, probably corresponding to the alpha-subunit of the insulin receptor and a major band with a molecular mass of 145 kDa for the alpha-subunit of the IGF-I receptor. Both insulin and IGF-I stimulated the incorporation of [3H]thymidine into DNA. A half-maximal effect was obtained at 1.6 x 10(-8) M for insulin and 1.2 x 10(-9) M for IGF-I. No additive effect on DNA synthesis was observed. Insulin at 8 x 10(-10) M increased the accumulation of [14C]glucose in mesangial cells, whereas IGF-I was 10-fold less potent.
Arnqvist
H J
HJ
Research Division, Joslin Diabetes Center, Boston, Massachusetts.
Ballermann
B J
BJ
King
G L
GL
D000818:Animals; D003432:Cross-Linking Reagents; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D003432:Cross-Linking Reagents; D007328:Insulin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D011972:Receptor, Insulin; D005947:Glucose; D013936:Thymidine