Adipocyte insulin binding and insulin action in chronic renal failure before and during continuous ambulatory...

In order to investigate the cellular mechanisms of the insulin resistance displayed by subjects with chronic renal failure, adipocyte insulin receptor status and in vitro insulin sensitivity were studied. Adipocytes from uremic subjects displayed normal maximum specific insulin binding (2.55 +/- 0.23 v 2.57 +/- 0.09% per 10 cm2 cell membrane, although half-maximum binding was observed at 91 +/- 8 (uremic) and 139 +/- 11 (control) pmol/L (P less than 0.005). In six subjects restudied after three months of continuous ambulatory peritoneal dialysis, maximum specific insulin binding fell as a consequence of changes in both receptor affinity and number (2.87 +/- 0.20 v 2.05 +/- 0.17% per 10 cm2 cell membrane, P less than 0.01). Basal and maximal rates of lipogenesis were similar in the uremic and control groups, and half-maximal stimulation occurred at 13.5 +/- 4.4 and 21.4 +/- 3.0 pmol/L, respectively (NS). During continuous ambulatory peritoneal dialysis, adipocyte insulin sensitivity did not change significantly as assessed by stimulation of lipogenesis or glucose uptake (half-maximal stimulation at 12.0 +/- 4.0 v 26.4 +/- 11.0 and 23.1 +/- 7.1 v 29.0 +/- 7.5 pmol/L, before and during dialysis, respectively). These data suggest either that adipose tissue and muscle display differential insulin sensitivities in chronic renal failure or that other factors such as circulating inhibitors of insulin action are not detected by in vitro assays.