Identification of The Downregulation of TPD52-Like3 Gene and NKX2-1 Gene in Type 2 Diabetes Mellitus Via RNA Sequencing

Abstract

In an earlier study, it was proposed that the final consequence of hereditary anomaly results in the development of type 2 diabetes, which already emerges in the prediabetic phase. It was thought to occur due to an increased flux, as compared to the healthy controls where protons (H + -ions) from the mitochondrial intermembranespace re-enter the matrix via uncoupling protein-1 (UCP1). This causes hyperthermia in and around the mitochondria [1].But the key question that remains to be answered here is for the connection between the increased flow of protons and type 2 diabetes mellitus. In the past decade, a study reported on the visual documentation of the possible interaction of lipid droplets with mitochondria. This interaction was found to be quite intimate with the involvement of membrane attached receptor proteins such as SNAP23 [2]. Also, the cellular population of mitochondria in brown adipocytes tissue could be divided into two subpopulations; i.e. mitochondrial population having physical evidence of adherence to a lipid droplet or peridroplet mitochondria, and a non-lipid droplet-bound cytoplasmic mitochondrial population without any adherence to lipid droplets [3,4].Although both the peridroplet mitochondria and cytoplasmic mitochondria are similar in their cell membrane composition they differ in other fundamental respects [3,4]. A comparison of the purified peridroplet mitochondria to cytoplasmic mitochondria suggests that peridroplet mitochondria are more elongated, whereas cytoplasmic mitochondria tend to be smaller. Also, peridroplet mitochondria have enhanced oxidative phosphorylation capacity, TCA cycle activity, ATP synthesis, as well as increased ATP-dependent triglyceride synthesis compared to cytoplasmic mitochondria. The measured fatty acid-driven respiration and UCP1 content in the isolated mitochondria suggests that for thermogenic fat oxidation peridroplet mitochondria are not specialized compared to cytoplasmic mitochondria [3]. This signifies that, under healthy conditions, in the peridroplet mitochondria the protons derived from free fatty acids (FFAs) and generated by the electron-transport chain during the oxidation process of FA are used for the production of ATP without any escape of protons via UCP1 to produce heat. On the other hand, the protons generated by the oxidation of cytoplasmic mitochondrial FA are mainly used for the production of heat. So, peridroplet mitochondria have an

The Evolution of Type 2 Diabetes Mellitus and Insulin Resistance

“…TPD52, TPD52L1, TPD52L2, and TPD52L3 [8,9]. When analyzing TPD52 and TPD52L3 genes, researchers found that the two sequencers shared 63 identical positions and 42 similar positions, resulting in an overall homology of 67.9% (Figure 1) [10]. Indeed, based on the high sequence homology with TPD52L3, it appears plausible that the primary function of TPD52L3 is lipid storage in adipose cells.…”

“…These results imply that a decrease in the unsaturation index in individuals with prediabetes or type 2 diabetes mellitus has the potential to translate into an increase in attractive forces between the mutual membrane phospholipid acyl chains, which redistributes the lateral pressure profile of the cell membrane [27]. This redistribution induces alterations in mechanical and biochemical properties of the glucose transport channel proteins, i.e., it reduces the pore diameter, which in turn, reduces the rate of glucose transport across the cell membrane, and therefore causes the onset of type 2 diabetes mellitus [10].…”