Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women

Abstract

BACKGROUND: The cell functions involved in the action of insulin Ð receptor binding, enzyme and transporter activities Ð are controlled by membrane properties. We have previously shown that the fasting plasma insulin (FPI) concentration and the homeostasis model assessment (HOMA) estimate of insulin resistance are associated with the sphingomyelin concentration in the erythrocyte membranes of obese women. OBJECTIVES: (1) To study the distribution of phospholipid classes in the plasma membrane and their association with insulin resistance markers in the adipocyte, an insulin-sensitive cell in obese women. (2) To investigate the in¯uence of diabetes in a small group of obese women treated by diet alone. (3) To compare the distribution of phospholipids in erythrocyte membranes in a subgroup of obese nondiabetic and diabetic women. SUBJECTS: Subcutaneous fat biopsies were taken from the abdominal region of 19 obese non-diabetic and seven obese type 2 diabetic women. Erythrocyte membrane assessment was performed in a subgroup of 10 of the 19 obese nondiabetic and in the seven diabetic patients. METHODS: The phospholipid composition of adipocyte and erythrocyte plasma membranes was analyzed by high performance liquid chromatography. RESULTS: FPI was positively correlated with the adipocyte membrane contents of sphingomyelin (P`0.001), phosphatidylethanolamine (P`0.05), and phosphatidylcholine (P`0.01) in the obese nondiabetic women. Similar correlations were obtained with HOMA. A stepwise multiple regression analysis indicated that sphingomyelin accounted for 45.6 and 43.8% of the variance in FPI and HOMA values as an independent predictor. There was a similar positive independent association between FPI and SM in the erythrocyte membranes of the studied subgroup. Diabetes per se did not in¯uence the independent association between SM membrane contents and FPI in both cell types. CONCLUSION: These results suggest a link between membrane phospholipid composition, especially SM, and hyperinsulinemia in obese women. International Journal of Obesity (2000) 24, 1600±1607 Keywords: obesity; type 2 diabetes; hyperinsulinemia; adipocyte; erythrocyte; plasma membrane; phospholipid classes IntroductionLow insulin sensitivity is common in obese individuals and is primarily due to defects in the pathway of insulin action in target tissues: muscle, liver and adipose tissue. It has been suggested recently that insulin resistance is associated with alterations in cell membrane properties. 1,2 Recent studies have demonstrated relationships between the fatty acid composition of phospholipids in skeletal muscle and the action of insulin. 3 ± 8 We have previously shown that changes in the distribution of phospholipid classes of the erythrocyte membrane were also associated with fasting plasma insulin (FPI) concentration and the homeostasis model assessment (HOMA) estimate of insulin resistance in 69 obese nondiabetic normoglycemic women. The most insulin resistant patients had the highest erythrocyte membrane sphingomyelin content....

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