Summary
The receptor binding and biological potency of despentapeptide insulin (DPI) was assessed in human adipocytes, rat adipocytes and rat hepatocytes. DPI displayed a lower affinity for binding to both human adipocytes (half-maximum displacement at 0.89 ± 0.04 and 0.20 ± 0.02 nmol/l for DPI and insulin respectively; P < 0.001) and rat adipocytes (half-maximum displacement at 7.12 ± 1.06 and 1.14 ± 0.18 nmol/l respectively, P < 0.05). However, although DPI was less potent than unmodified insulin in stimulating glucose uptake in rat adipocytes (half-maximal stimulation at 2.0 ± 0.67 and 0.47 ± 0.18 nmol/l respectively; P < 0.05), DPI was equipotent with insulin in human adipocytes (half-maximal stimulation at 0.034 ± 0.001 and 0.027 ± 0.001 nmol/l respectively; P > 0.2). In rat hepatocytes, DPI was twofold less potent in binding displacement activity (half-maximum displacement at 3.8 ± 0.9 and 1.7 ± 0.3 nmol/l respectively; P < 0.01) but appeared to be equivalent in stimulating amino butyric acid uptake (half-maximum stimulation at 0.98 ± 0.12 and 0.95 ± 0.26 nmol/l respectively). The difference in affinity of DPI binding to rat liver membranes was less marked (1.3 fold decreased compared with insulin: 5.3 ± 0.7 and 4.2 ± 0.6 nmol/l respectively; P < 0.001).
Thus, the decreased receptor affinity of DPI was reflected in decreased biological potency in rat adipocytes, but not in human adipocytes nor rat hepatocytes. These data suggest differences in the binding-action linking in the cells of different tissues and different species.
Key words
Insulin Analogue - Despentapeptide Insulin - Insulin Binding - Insulin Action
