**6. Others**

#### **6.1. Glucose transporters**

Glucose transporters (GLUT) are integral membrane proteins that mediate the transport of glucose and structurally-related substances across the cellular membranes [67].

Sugar transport catalyzed by 11 out of 14 members of the human GLUT family. There are specific characteristics of each isotypes. They are different in expression profile, substrate specificity and kinetic characteristics. Therefore, the tissue adaptation of the glucose uptake will be determined and regulated by specific tissue gene expression. GLUT4 malfunction in expression or regulation contributes to IR while GLU2 plays a role in hormonal and neuronal control by acting a glucose sensor in β-cells of the pancreas and neuronal cells [68]. GLUT1 is ubiquitously expressed with particularly high levels in human erythrocytes and in the endothelial cells lining the blood vessels of the brain. GLUT3 is expressed primarily in neurons and, together, GLUT1 and GLUT3 allow glucose to cross the blood-brain barrier and enter neurons [69].

The GLUTI, GLUT2, and GLUU3 are the major glucose transporters isoforms present in these cells and they are constitutively localized to the plasma membrane. The glucose flux across the membrane is largely dependent upon the circulating blood glucose level or concentration. In acute state, the glucose regulated the transport system in the muscles and fat cells responded within minutes to insulin [70].

GLUT4 is the primary hormonally-responsive transporter and it is the major insulin-respon‐ sive transporter [69]. GLUT4 expression is also reduced by low insulin states, such as in muscle during fasting, and in IR adipose tissue [71]. The malfunction of glucose transporter expression or regulation (GLUT4) appears to contribute to the IR syndrome [68].
