The effect of glibenclamide on plasma insulin, plasma somatomedin bioactivity and skeletal growth in hypophysectomized rats

Abstract

Abstract. Male rats, body weight 60–75 g, were hypophysectomized. Three days after operation the animals were divided into two groups. Group B received solvent solution and group C 1 mg/kg body weight per day of glibenclamide ip for the following 9 days. Group A consisted on non-operated normal rats. Twenty-four hours after the last injections and after a 12 h overnight fast the body weights of groups B and C were not different, the increase during the 10 days being 10% in both groups. Serum insulin (IRI) was significantly higher in group C than in group B (C: 8.0 ± 0.3 μU/ml, n = 14 vs B: 4.9 ± 1.0 μU/ml, n = 14; P < 0.01, mean ± sem) as was serum somatomedin bioactivity (SM)-porcine cartilage assay — (C: 1.06 ± 0.1 U/ml, n = 14 vs B:0.41 ± 0.01 U/ml, n = 14; P < 0.001). Skeletal growth was determined with the tibia test and by a radiograph of each rat. The width of the proximal epiphyseal growth plate of the tibia was significantly increased in group C compared to group B (C: 204 ± 4.8 μm, n = 12 vs 181 ± 6.5 μm, n = 13; P < 0.005). On the radiograph the area of the right femur was not different between the two groups of animals, while the height and the area of the first lumbar spine were significantly augmented in group C. The results show that glibenclamide stimulates IRI, SM and skeletal growth in hypophysectomized rats. Compared to the glibenclamide treated hypophysectomized animals the normal rats of group A had doubled their body weights. IRI (59 ± 5 μU/ml, n = 4) and skeletal growth (tibia test: 454 ± 5.8 μm) were greatly increased. SM did not differ between group A (1.21 ± 0.35 U/ml and group C. T4 was much lower in group B (0.64 ± 0.09 μg/100 ml, n = 5) than in group A (4.1 ± 0.3 μg/100 ml, n = 6; P < 0.001). It is concluded that a normal SM concentration is not necessarily associated with appropriate growth.