Free fatty acids, glucose, and insulin in type 2 diabetes mellitus

Abstract

Xu et al used the HOMA2 model to estimate the β-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels. This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities, which led to type 2 diabetes. However, significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids (FFAs) into the blood circulation, which leads to a marked reduction in membrane flexibility. These data favor a FFA-glucose-insulin axis. The authors are invited to extend their study with the introduction of the saturation index (number of carbon-carbon double bonds per 100 fatty-acyl chains), as observed in erythrocytes.

Keywords: Free fatty acids; Membrane flexibility; NKX2-1 gene; RNA sequencing; Type 2 diabetes; TPD52L-3 gene; Unsaturation index

Core Tip: A substantial reduction in both NKX2-1 and TPD52L3 proteins is largely responsible for a reduction in carbon-carbon double bonds of phospholipids which, in turn, translates into the redistribution of the lateral pressure profile, and thereby reduces the transport speed of glucose molecules across the cell membrane. Consequently, the amount of plasma glucose entering the β-cell via GLUT2 gives a false negative result. Also the redistribution of the lateral pressure profile lowers the insulin release from β-cells into the blood circulation. Both phenomena cause the onset of type 2 diabetes mellitus.