Abstract
Pancreatic β-cells and the liver play a key role in glucose homeostasis. After a meal or in a state of hyperglycemia, glucose is transported into the β-cells or hepatocytes where it is metabolized. In the β-cells, glucose is metabolized to increase the ATP:ADP ratio, resulting in the secretion of insulin stored in the vesicle. In the hepatocytes, glucose is metabolized to CO2, fatty acids or stored as glycogen. In these cells, solute carrier family 2 (SLC2A2) and glucokinase play a key role in sensing and uptaking glucose. Dysfunction of these proteins results in the hyperglycemia which is one of the characteristics of type 2 diabetes mellitus (T2DM). Thus, studies on the molecular mechanisms of their transcriptional regulations are important in understanding pathogenesis and combating T2DM. In this paper, we will review a recent update on the progress of gene regulation of glucose sensors in the liver and β-cells.
Highlights
Glucose is one of the most important molecules that acts as a basic fuel for energy source and a substrate for intermediary metabolism as well
Blood glucose is transported into the liver and β-cells of pancreas through solute carrier family 2 (SLC2A2, known as GLUT2) and immediately phosphorylated by glucokinase present in the liver (LGCK) or β-cells which acts as a glucose sensor
We have identified a sterol regulatory element binding transcription factor 1 (SREBF1) response element (SRE) in the promoter of mouse Slc2a2 gene, which is responsive to glucose in primary cultured hepatocytes [69]
Summary
Glucose is one of the most important molecules that acts as a basic fuel for energy source and a substrate for intermediary metabolism as well. Glucose-6-phosphate in the hepatocytes undergoes glycolysis, glycogenesis, pentose phosphate pathway, or hexosamine biosynthetic pathway depending on the metabolic needs Both SLC2A2 and GCK have high Km values and high capacity and are able to sense and transport glucose into hepatocytes or β-cells in proportion to the blood glucose level [2]. Most of the type 2 diabetes mellitus (T2DM)-associated genes are mainly involved both in β-cell function and peripheral insulin sensitivity. (NEUROD1) [6,7,8] These transcription factors are known to be involved in the regulation of tissue-specific expression of SLC2A2 and/or GCK genes [9]. The gene expression of SLC2A2 and GCK is affected by metabolic conditions and are tissue-specific. Studying the molecular mechanisms in relation to T2DM will help understand its pathogenesis and find potential drug targets for the development of therapeutic drugs
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