SATURATED FATTY-ACID INDUCED INSULIN-RESISTANCE IN RAT ADIPOCYTES

被引:124
作者
HUNNICUTT, JW [1 ]
HARDY, RW [1 ]
WILLIFORD, J [1 ]
MCDONALD, JM [1 ]
机构
[1] UNIV ALABAMA, DEPT PATHOL,701 S 19TH ST,LHR BLDG,ROOM 509, BIRMINGHAM, AL 35294 USA
关键词
D O I
10.2337/diabetes.43.4.540
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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), 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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页码:540 / 545
页数:6
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