AJP - Endocrinology and Metabolism, Vol 241, Issue 4 281-E290, Copyright © 1981 by American Physiological Society
Effect of liposome-adipocyte interaction on hexose uptake and insulin action
A. Sandra and D. J. Fyler
The effect of unilammelar lipid vesicles composed of defined acyl chain
phosphatidylcholines or binary vesicles comprised of dioleoyl
phosphatidylcholine (DOPC) and a variety of other lipid species on insulin
action in isolated rat adipocytes was studied. Cells were treated with
vesicles and subsequently analyzed for basal and insulin-stimulated hexose
uptake. Of the different vesicles tested, only those containing DOPC and
phosphatidylserine (PS) markedly inhibited the effect of insulin. The
inhibition was a function of PS concentration in the binary vesicle. Basal
uptake, on the other hand, was stimulated by PS-containing vesicles. The
changes in insulin-stimulated hexose uptake following interaction of
adipocytes with DOPC-PS vesicles were accompanied by alterations in the
Vmax of the uptake process and in affinity of insulin binding, although the
similar ED50 values of the control and vesicle-treated groups suggest that
the observed effects on insulin sensitivity may be mediated by an
uncoupling of the insulin receptor from transport activation. Several lines
of evidence are consistent with vesicle-cell fusion as the pathway of
DOPC-PS uptake under these conditions. Fluorescence microscopic analysis of
fat cells following their interaction with vesicles filled with fluorescent
dye indicated that the internal contents of the adipocytes became generally
labeled. Biochemical studies of cell fractionation after the interaction of
adipocytes with radiolabeled vesicles and effects of metabolic inhibitors
and cell fixatives on vesicle uptake also support the fusion pathway.
