Possible involvement of corticosterone in bone loss of genetically diabetic db/db mice.
The etiology of bone loss in non-insulin dependent diabetes mellitus is still unknown. We compared serum biochemical parameters and bone parameters of genetically diabetic db/db mice with those of their control non-diabetic +/+ mice. We found that serum corticosterone levels of the db/db mice were significantly elevated after 5 weeks while bone mineral density of femur metaphysis significantly decreased in the db/db mice after 12 weeks of age compared with age matched +/+ mice. To explore the causal relationship between the serum corticosterone levels and the bone loss, metyrapone (100 mg/kg, p.o., twice a day), a glucocorticoid synthesis inhibitor, was administered to these mice for 4 weeks after the age of 8 weeks. The compound significantly decreased serum corticosterone levels in both strains. Metyrapone prevented bone loss by increasing the bone mineral content of the metaphysis in the db/db mice. In addition, the treatment slightly improved the ratio of ash weight to dry weight in the db/db mice. These results suggest that increased serum corticosterone levels are concerned with the etiology of bone loss in non-insulin dependent diabetic db/db mice.
Takeshita
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N
Department of Biological Sciences, Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. nobuaki_takeshita@po.fujisawa.co.jp
Yoshino
T
T
Mutoh
S
S
D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D002118:Calcium / Q000493:pharmacokinetics; D003345:Corticosterone / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005269:Femur; D007328:Insulin / Q000097:blood; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D007328:Insulin; D002118:Calcium; D003345:Corticosterone; D008797:Metyrapone