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[Altered bone metabolism in db/db mice]
1Third Department of Internal Medicine, Tokyo Medical and Dental University.
Abstract:
Bone and calcium metabolism was investigated in genetically obese, diabetic db/db mice and compared with that in a new hypoglycemic agent (AS-6) treated db/db mice and in their lean litter mates as controls. The 5-week-old db/db mice (serum Ca 9.88 +/- 0.22 mg/dl, glucose 258.6 +/- 13.3 mg/dl) were randomly divided into two groups. One group, together with their lean litter mates, was fed a commercial diet (CE-2). The other db/db group was fed CE-2 diet containing 0.1% of AS-6. Both groups were fed for 20 weeks. The serum glucose and calcium levels in db/db control groups (serum Ca 12.3 +/- 0.1 mg/dl, glucose 650.2 +/- 23.9 mg/dl) were higher than those in lean control groups (Ca 9.8 +/- 0.2 mg/dl, glucose 180.7 +/- 10.1 mg/dl). The wet, dry and ashed weights of the femur in db/db control were significantly lower and the length of femur in db/db control was significantly shorter than those of lean controls. These data suggest that retarded bone growth in db/db mice is related to progression of diabetes. Although, there was no change in Ca/P, Ca/ash and total perimeter in femurs, the cortical area in the femurs of db/db control mice (0.65 +/- 0.02 mm2) was significantly smaller than that of the femurs of lean control mice (0.74 +/- 0.02 mm2). The cortical bone thinning observed in the db/db control could have been caused by increased bone resorption. Treatment with AS-6 for 20 weeks resulted in a 48.6% decrease of serum glucose and 5.2% decrease of calcium as compared with db/db controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study shows that diabetes in db/db mice leads to retarded bone growth and thinner cortical bone. Treatment with the hypoglycemic agent AS-6 improved glucose and calcium levels, suggesting a link between diabetes control and bone health.
Area of Science:
- Metabolic disorders
- Bone metabolism
- Pharmacology
Background:
- Genetically obese, diabetic db/db mice exhibit altered bone and calcium metabolism.
- Diabetes progression is associated with retarded bone growth and cortical bone thinning in these mice.
Purpose of the Study:
- To investigate the effects of a novel hypoglycemic agent, AS-6, on bone and calcium metabolism in diabetic db/db mice.
- To compare metabolic and bone parameters between treated db/db mice, untreated db/db mice, and lean controls.
Main Methods:
- db/db mice and lean controls were fed a standard diet (CE-2) for 20 weeks.
- A separate group of db/db mice received the CE-2 diet supplemented with 0.1% AS-6.
- Serum glucose and calcium levels, as well as femur weights and dimensions, were analyzed.
Main Results:
- db/db mice showed significantly higher serum glucose and calcium levels, lower femur weights, and shorter femur length compared to lean controls.
- Cortical bone area was significantly smaller in untreated db/db mice, suggesting increased bone resorption.
- AS-6 treatment reduced serum glucose by 48.6% and serum calcium by 5.2% compared to untreated db/db mice.
Conclusions:
- Retarded bone growth in db/db mice is linked to diabetes progression.
- AS-6 demonstrates potential in managing hyperglycemia and improving calcium balance in diabetic mice.
- Further research is warranted to explore AS-6's therapeutic potential for bone health in diabetes.