Letter to the Editor
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2022; 13(3): 275-277
Published online Mar 15, 2022. doi: 10.4239/wjd.v13.i3.275
Free fatty acids, glucose, and insulin in type 2 diabetes mellitus
Rob NM Weijers
Rob NM Weijers, Teaching Hospital, OLVG, Amsterdam 95500, Netherlands
Author contributions: Weijers RNM solely contributed to this paper.
Conflict-of-interest statement: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rob NM Weijers, PhD, Teacher, Teaching Hospital, OLVG, Oosterpark 9, 1091 AC Amsterdam 9, Amsterdam 95500, Netherlands. robw01@xs4all.nl
Received: September 23, 2021
Peer-review started: September 23, 2021
First decision: November 8, 2021
Revised: December 24, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 15, 2022
Processing time: 173 Days and 1.1 Hours
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.