Uses of knockout, knockdown, and transgenic models in the studies of glucose transporter 4

Abstract

Currently, glucose transporter 4 (GLUT4) has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose tissues. The development of recombinant DNA techniques allows the creations of genetically knockout, knockdown and transgenic animals and cells for the study of GLUT4’s physiological functions. Here, we have used key words to search the PubMed and summarized the methods used in Slc2a4 gene knockout, GLUT4 knockdown and overexpression in the whole body and tissue specific manner. The whole body GLUT4-null mice have growth retardation, but normal glucose tolerance and basal glucose turnover rates. Compared with whole body Slc2a4 knockout mice, adipose and muscle double knockout mice have impaired insulin tolerance and glucose intolerance. The results of GLUT4 knockdown in 3T3-L1 adipocytes have shown that its expression is needed for lipogenesis after, but not during, differentiation. Transgenic mice with the whole body GLUT4 overexpression have normal body weight and lowered blood glucose level. The adipose tissue specific overexpression of GLUT4 leads to increases in mouse body weight and adipose tissue weight. The insulin-stimulated GLUT4 translocation in the skeletal muscle contributes to the regulation of glucose homeostasis. Data from both transgenic overexpression and tissue specific Slc2a4 knockout indicate that GLUT4 probably plays a role in the glucose uptake in the fasting state. More studies are warranted to use advanced molecular biology tools to decipher the roles of GLUT4 in the control of glucose homeostasis.

Keywords: Glucose transporter 4; Knockout; Knockdown; Transgene; Overexpression; Insulin

Core Tip: The whole body glucose transporter 4 (GLUT4)-null mice have growth retardation, but normal glucose tolerance and basal glucose turnover rates. The muscle-specific GLUT4 knockout mice have normal body weight and fat pad weight at least before 6 mo of age, whereas the adipose-GLUT4 knockout mice have glucose intolerance. The adipose and muscle GLUT4 double knockout mice develop hyperglycemia in the fasting state, suggesting the role of GLUT4 in fasting state. Compared to the control mice, wholebody GLUT4 transgenic mice have similar growth rate before 10 wk of age, lower blood glucose in the fasting, and lower insulin level in the fed state. The adipose tissue specific GLUT4 overexpression increases body weight, glucose transport rate and adipose tissue weight. Data from both transgenic overexpression and tissue specific knockout of GLUT4 indicate that GLUT4 probably plays a role in the glucose uptake in the fasting state.