Decreased osteoblast activity in spontaneously diabetic rats. In vivo studies on the pathogenesis.
Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused by serum-borne factors. To explore its pathogenesis, we carried out experiments in diabetic and nondiabetic BB rats, using plasma osteocalcin concentrations (OC) as a marker for osteoblast activity. In nondiabetic rats, the i.v. infusion of glucose (30%, 4 d) did not change OC; s.c. insulin infusion (4 U/d, 14 d) reduced OC by 27% (p < 0.01). In diabetic rats, OC were decreased from the first day of glycosuria (71 +/- 5% of paired controls), declining exponentially to 24 +/- 3% after 5 wk. Insulin infusion (1, 2, and 3 U/d, 14 d) produced gradual restoration of OC. OC were better correlated with insulin-like growth factor-I (IGF-I) than with insulin levels in these experiments. OC were dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73 +/- 8 vs 22 +/- 4 micrograms/L before ADX; p < 0.001), but not if corticosterone was administered. Ligand blotting of IGF binding proteins showed a marked decrease in two bands (44-49 and 32-35 kDa) 10-14 d after diabetes onset; the density of these bands was increased, but not normalized after ADX. Thus, decreased osteoblast activity is present from the onset of diabetes, is dependent on endogenous corticosterone, and cannot be reproduced by hyperglycemia in nondiabetic rats.
Verhaeghe
J
J
Department of Obstetrics and Gynecology, Katholieke Universiteit Leuven, Belgium.
Van Herck
E
E
van Bree
R
R
Moermans
K
K
Bouillon
R
R
D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D006029:Glycosuria / Q000097:blood; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010006:Osteoblasts / Q000502:physiology*; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D011913:Rats, Inbred BB
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D003345:Corticosterone