MODULATION OF THE ACTIVITY OF GLUCOSE TRANSPORTERS (GLUT) IN THE AGEDOBESE RAT ADIPOCYTE - SUPPRESSED FUNCTION, BUT ENHANCED INTRINSIC ACTIVITY OF GLUT

To study the contribution of glucose transporters (GLUT) to insulin re sistance in aging, GLUT intrinsic activity was assessed in a cell-free system. Adipocytes were isolated from 18-month-old rats and young con trols and incubated either with or without 7 nM insulin. Plasma membra ne (PM) and low density microsomal fractions were prepared from the ce lls, and GLUT levels were assessed in these fractions before and after reconstitution into liposomes. Glucose transport rates were measured in intact cells and liposomes. Functional and intrinsic activities of GLUT were assessed from the ratio between these transport rates and GL UT levels in the respective fractions. Basal 3-O-methylglucose transpo rt rates were unaffected by aging, which is consistent with unchanged levels of GLUT in PM. Insulin-stimulated glucose transport was 60% low er in aging, as was the extent of GLUT recruitment to PM. The effect o f insulin stimulation of GLUT functional activity by 6-fold at PM was attenuated by 40% in aging. Conversely, the basal intrinsic activity o f GLUT was significantly enhanced in aging (by 280% and 230% in PM and density microsomal liposomes, respectively) and was further stimulate d by insulin by about 160% in PM, compared to only about 117% stimulat ion in controls. In conclusion, our data show that insulin stimulates the intrinsic activity of GLUT in rat adipocytes, and this activity is further enhanced in aging. Impaired glucose uptake in aging can be at tributed to depleted GLUT4 levels and impaired function of GLUT at the cell surface. The discrepancy observed between impaired function and enhanced intrinsic activity of GLUT suggests the presence of additiona l factors that modulate the full functional expression of GLUT at the cell surface.