The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats.
Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone formation/turnover. In this study, male diabetic BB rats were infused intraperitoneally or subcutaneously for 2 weeks with hormones that are believed to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4 U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor-I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body weight per day). Saline-treated diabetic BB rats had decreased plasma concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8 (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface, and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day). Testosterone and hGH infusions had no effect on weight loss or on decreased skeletal growth and bone formation of diabetic rats, nor did they increase plasma IGF-I concentrations. Insulin infusions into diabetic rats resulted in hyperinsulinaemia and accelerated weight gain. The epiphyseal width, osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats doubled but did not restore plasma IGF-I levels to normal; weight gain, however, was similar to that in control rats. IGF-I treatment had no effect on epiphyseal width, osteoblast/osteoid surfaces and OC concentrations, but improved the decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)
Verhaeghe
J
J
Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Belgium.
Suiker
A M
AM
Visser
W J
WJ
Van Herck
E
E
Van Bree
R
R
Bouillon
R
R
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology; D013977:Tibia / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D007328:Insulin; D015675:Osteocalcin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone