Regulation of glucose transport by insulin and non-hormonal factors

Abstract

Glucose uptake by nucleated cells is mediated by facilitated diffusion. In adipocytes, fibroblasts and muscle fibers uptake is regulated by a variety of hormones, environmental factors, and metabolic conditions. Glucose uptake by mammalian red cells also occurs by facilitated diffusion, but is not regulated by the same factors and conditions as in nucleated cells; yet the pharmacological and selectivity properties of this transport system resemble those of glucose uptake in regulated cells. The glucose transporter in the human red cell is a 55, 000 dalton protein, which has been purified to homogeneity and functionally reconstituted in artificial systems. Little is known about the molecular identity of the sugar carrier in other cell types. Glucose uptake is stimulated by insulin in muscle, fat and skin cells but not in bone, brain, placenta, erythrocytes nor probably lymphocytes. In responsive cells, stimulation occurs within seconds of exposure to the hormone; it requires cellular integrity but once elicited, it persists in isolated membranes; protein synthesis is not required for either the onset of the response or the return to basal conditions after hormone removal; on the other hand, intracellular energy is required for both steps; the cytoskeleton does not seem to be involved in the regulation of glucose uptake by insulin. In general, insulin increases V t while K t is unaffected. The hormone could affect the rate of turnover of the transporter in the membrane, and/or the number of transporters active at any time. An increase in the number of transport sites in the plasma membrane, due to incorporation of additional sites originating from intracellular membranes, has recently been proposed on the basis of both 3H-cytochalasin B binding and glucose transport determinations in isolated plasma and intracellular membranes. The feasibility and implications of a rapid and reversible translocation of glucose transport sites from specific intracellular pools to the plasma membrane are discussed.