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.

Molecular Structures of Fluid Phosphatidylethanolamine Bilayers Obtained from Simulation-to-Experiment Comparisons and Experimental Scattering Density Profiles

“…A recent example has been the unraveling of the so-called Gordian knot of type 2 diabetes mellitus, where the occurrences of gestational diabetes mellitus were correlated with a markedly lower PC and PE unsaturation index. 8 PCs are the major lipid group in mammalian membranes, while PEs account for nearly 25% of total phospholipids (up to 45% of the brain's total lipid content), and are the major constituent of bacterial membranes. 9 PE was first isolated by Ludwig Thudichum in 1884, at which time the discovery's impact was considered to be hardly commensurate with the expended time and cost"not unlike today's sentiments applied to basic research" as noted by Vance and Tasseva.…”

Mammalian phospholipid homeostasis: evidence that membrane curvature elastic stress drives homeoviscous adaptation in vivo

“…In a broader context, altered lipid compositions are associated with a number of diseases such as cancer [31], obesity [32], Alzheimer's disease [33], liver disease [34] and type 2 diabetes [35]. Therefore, quantitative system models of cellular phospholipid homeostasis are critical to understanding these pathologies.…”

Deleterious effects of lard-enriched diet on tissues fatty acids composition and hypothalamic insulin actions

“…The SFA geometrical configuration increases membrane phospholipid rigidity and lipid bilayer tension, which impairs GLUT4 vesicle exteriorization, resulting in glucose intolerance (21,52). Diabetes-induced glucotoxicity contributes to β-cells failure, and exposing cultured human pancreatic islets to MUFAs reduced apoptosis induced by high glucose and palmitic acid levels (53).…”