Palmitate has been shown to stimulate glucose transport, translocation of GLUT4 and insulin receptor autophosphorylation in isolated rat adipocytes (Biochem Biophys Res Commun 177:343–49, 1991). Here we further characterize the ability of short-term treatment with free fatty acids to stimulate glucose transport in isolated rat adipocytes and demonstrate that prolonged treatment induces insulin resistance. Treatment of adipocytes for 15 min with 1 mM myristate (14:0), palmitate (16:0), or stearate (18:0) stimulates glucose transport by 119 ± 33, 89 ± 29, and 114 ± 30%, respectively. In contrast, oleate (cis 18:1), 1), elaidate (trans 18:1), and linoleate (cis 18:2) do not stimulate glucose transport. Palmitate stimulates glucose transport in a concentration-dependent manner, demonstrating saturation at 1 mM and half-maximal stimulation at 0.25–0.5 mM. Prolonged treatment (4 h) of rat adipocytes with 1 mM palmitate induces insulin resistance. After a 4-h preincubation with palmitate (1 mM), insulin stimulates glucose transport in rat adipocytes by 4.4-fold ± 0.8, vs. 8.8-fold ± 0.8 in controls (n = 3). Palmitate-induced resistant cells demonstrated a 40% inhibition in maximal insulin responsiveness with little change in insulin sensitivity. Insulin binding is only slightly decreased (8%) in palmitate-pretreated cells. These studies indicate that saturated fatty acids stimulate glucose transport acutely and on prolonged exposure induce insulin resistance via a post-insulin binding defect. The underlying molecular mechanisms of insulin resistance induced by prolonged treatment with saturated fatty acids may now be investigated using this unique cellular model.
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Original Contributions| April 01 1994
Saturated fatty Acid–Induced Insulin Resistance in Rat Adipocytes
John W Hunnicutt;
Robert W Hardy;
Address correspondence and reprint requests to Dr. Jay M. McDonald, Department of Pathology, University of Alabama at Birmingham, 701 South 19th Street, LHR Building, Room 509, Birmingham, AL 35294.
John W Hunnicutt, Robert W Hardy, Jodie Williford, Jay M McDonald; Saturated fatty Acid–Induced Insulin Resistance in Rat Adipocytes. Diabetes 1 April 1994; 43 (4): 540–545. https://doi.org/10.2337/diab.43.4.540
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