Effects of cell volume on insulin binding, internalization and degradation in rat adipocytes.
Adipocytes from old rats (greater than 450 g) were separated into 2 populations with mean cell volumes of 201 +/- 14 and 813 +/- 41 pl (mean +/- SEM, 20 observations) by filtering through nylon mesh (64 microns diameter) and compared with adipocytes from young rats (less than 150 g) with a mean adipocyte volume of 154 +/- 20 pl (14 observations). Large adipocytes had more insulin receptors per cell but less per unit of surface area. They internalized greater amounts of insulin than small cells in the presence or absence of bacitracin and chloroquine, although the proportion of bound hormone which was internalized was similar in all 3 groups. Down-regulation of the insulin receptor was evident in large and small adipocytes after incubation in the presence of 10(-7)M insulin. Large cells degraded insulin (extracellularly and intracellularly) at significantly greater rates than small cells whether expressed per cell or per unit of surface area. Small cells from old rats had essentially identical properties to small cells from young rats in all parameters examined. The results suggest that the decreased surface density of insulin receptors observed in large adipocytes from old rats is due to size rather than age and that the decreased insulin sensitivity of large adipocytes is not due to an inability to internalize insulin or down-regulate its receptors but may be due to increased rates of insulin degradation.
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000375:Aging; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007328:Insulin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D013997:Time Factors
D007328:Insulin; D001414:Bacitracin; D002738:Chloroquine; D011972:Receptor, Insulin