Reduced insulin binding to liver plasma membranes in inherently obese diabetic CBA/Ca mice

Insulin binding to isolated liver plasma membranes was measured in mice from C57BL and LACG strains, and in normal and obese diabetic mice from the Bristol CBA/Ca colony. A simple and rapid three-step method for the preparation and purification of liver plasma membranes, using Percoll density gradient centrifugation was used. Both high and low affinity binding was detected in membranes from all four groups of mice. The Kd values for binding were similar in all groups, but the insulin binding capacity (Bmax) at low and high affinity was significantly reduced in obese CBA mice compared to age-matched lean controls. It is proposed that insulin receptor down-regulation may account for the insulin resistance observed in spontaneously obese diabetic CBA mice.