Characterisation of mechanisms responsible for uraemic insulin resistance: in vitro experiments.

In an attempt to define the cellular basis of the uraemic insulin resistance we studied insulin action in adipocytes from eight patients with undialysed chronic uraemia and from eight matched healthy controls. (125I)-insulin binding to fat cells from uraemic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited a half-maximal response were 422 +/- 95 pmol/L in uraemic patients and 179 +/- 38 pmol/L in normals (p less than 0.01). The non-insulin and the maximally insulin stimulated glucose transport of adipocytes from uraemic patients was normal. The lipogenesis of fat cells from uraemic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmol/L in uraemic patients and at 11 +/- 3 pmol/L in normals, p less than 0.01) with unchanged non-insulin and maximally insulin stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uraemia may be primarily accounted for by post-binding defects localised to glucose transport and metabolism.