Hepatic adrenergic receptors in the genetically diabetic C57 BL/KsJ (db/db) mouse

Abstract

1. 1. At 30 weeks of age, homozygote diabetic C57 BL KsJ (db/db) mice were grossly obese, lethargic and displayed moderate hair loss relative to heterozygote control C 57 BL KsJ (db/+) mice. 2. 2. In diabetic mice, compared to control, the total body weights, liver weight: body weight ratios, and blood glucose levels were increased 2.3 fold, 20% and 3.1 fold, respectively. 3. 3. Analysis of plasma membranes isolated from control and diabetic mouse liver established that comparable purity levels were achieved since relative specific activities of the plasma membrane markers 5′-nucleotidase and γ-glutamyltranspeptidase were similar: 10.2 and 11.4 fold with respect to 5′-nucleotidase in control and diabetic states respectively; and 8.0 and 8.3 fold with respect to γ-glutamyltranspeptidase in control and diabetic states respectively. 4. 4. A select effect of diabetes on γ-glutamyltranspepetidase, however, was observed. The activity of this enzyme was found to be reduced 16% in diabetic liver compared to control liver. 5. 5. Assessment of [ 3H]prazosin and [ 3H]dihydrolalprenolol binding to mouse liver plasma membranes indicated that although there was no difference in β-adrenergic receptor binding in control and diabetic states, α 1-adrenergic receptor binding was found to be reduced 43% in diabetic mouse liver plasma membranes. 6. 6. Scatchard analyses of kinetic studies indicate that the reduction is a reflection of decreases in α 1-adrenergic receptor numbers with no change in α 1 receptor affinity in the diabetic state: since for diabetic and control liver plasma membranes, K d values were 3.40 ± 0.02 nM and 3.40 ± 0.01 nM respectively; and B max were 650.12 ± 16.44 fmol mg −1 and 380.76 ± 12.92 fmol mg −1, respectively.