Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus

Abstract

Identifying the causative relationship between the fatty acid composition of cell membranes and type 2 diabetes mellitus fundamentally contributes to the understanding of the basic pathophysiological mechanisms of the disease. Important outcomes of the reviewed studies appear to support the hypotheses that the flexibility of a membrane determined by the ratio of (poly)unsaturated to saturated fatty acyl chains of its phospholipids influences the effectiveness of glucose transport by insulin-independent glucose transporters (GLUTs) and the insulin-dependent GLUT4, and from the prediabetic stage on a shift from unsaturated towards saturated fatty acyl chains of membrane phospholipids directly induces a decrease in glucose effectiveness and insulin sensitivity. In addition, it has become evident that a concomitant increase in stiffness of both plasma and erythrocyte membranes may decrease the microcirculatory flow, leading ultimately to tissue hypoxia, insufficient tissue nutrition, and diabetes-specific microvascular pathology. As to the etiology of type 2 diabetes mellitus, a revised hypothesis that attempts to accommodate the reviewed findings is presented.

Fig. (1)

Schematic representation of part of a lipid bilayer. A represents the interfacial area A per lipid molecule, that is, the surface of the cross-section of the cylindrical part of the phospholipid molecule, and D_HH the head–head distance across the lipid bilayer.

Fig. (2)

Average interchain distances for the simulation of PEPC (■) and POPC (▲). PEPC: 1-palmitoyl-2-elaidoyl-phosphatidylcholine; POPC: 1-palmitoyl-2-oleoyl-phosphatidylcholine.

Fig. (3)

Hypothetical relationship between the ratio of cis fatty acid (cis FA) to total FA and the duration of the prediabetic stage. The cis FA/total FA ratio is that of PC and PE fatty acids in the erythrocyte membrane. At time 0, the value of the ratio represents the value for pregnant women with normal glucose tolerance and no inherited defect in mitochondrial oxidative phosphorylation. Reduction of the ratio below a critical value is postulated to result in overt type 2 diabetes mellitus. The distribution of the y axis values is based on previously published data [1]. The ratio is assumed to decrease in pregnant women because of increased plasma saturated free fatty acid concentrations, resulting in mild gestational hyperglycemia, GDM, or type 2 diabetes mellitus.

Fig. (4)

Revised hypothetical steps in the development of type 2 diabetes mellitus.