Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease

Abstract

A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific glucose uptake and metabolism in the liver, skeletal muscle, and adipose tissue to ensure homeostatic control of blood glucose levels. Reduced glucose transport activity results in aberrant use of energy substrates and is associated with insulin resistance and type 2 diabetes. It is well established that GLUT2, the main regulator of hepatic hexose flux, and GLUT4, the workhorse in insulin-and contraction-stimulated glucose uptake in skeletal muscle, are critical contributors in the control of whole-body glycemia. However, the molecular mechanism how insulin controls glucose transport across membranes and its relation to impaired glycemic control in type 2 diabetes remains not sufficiently understood. An array of circulating metabolites and hormone-like molecules and potential supplementary glucose transporters play roles in fine-tuning glucose flux between the different organs in response to an altered energy demand.

Insulin‐dependent glucose consumption dynamics in 3D primary human liver cultures measured by a sensitive and specific glucose sensor with nanoliter input volume

“…36 Notably, while glucose transporters in other tissues, such as GLUT4 in skeletal muscle, are insulin sensitive, activity of the predominant hepatic glucose transporters GLUT1 and GLUT2, is not regulated by insulin. [37][38][39] However, despite the lack of glucose transporter regulation, overall hepatic glucose uptake is clearly insulin sensitive in humans in vivo, 40 at least in part due to the role of insulin in promoting intracellular glucose utilization and regulating hepatic glucose output through suppression of gluconeogenesis and glycogenolysis, which contributes to the maintenance of a steep glucose gradient and, in turn, facilitates influx. However, the detailed mechanisms underlying this insulin-dependent control of hepatic glucose uptake remain incompletely understood.…”

In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat

“…However, there was a positive correlation between redox ratio and GLUT1 gene expression (lower redox ratio and lower GLUT1 ), and a negative correlation between redox ratio and GLUT4 expression (higher redox ratio and lower GLUT4 ; Figure 3A,B). The GLUT1 gene encodes for glucose transporter 1, which in adipose tissue is slightly responsive to insulin, and the GLUT4 encodes for the highly insulin‐sensitive glucose transporter 4 [87]. In mature PAT, GLUT1 expression is much lower than GLUT4 both at the mRNA (Table 2) and protein level [88].…”

Viburnum stellato-tomentosum Extract Suppresses Obesity and Hyperglycemia through Regulation of Lipid Metabolism in High-Fat Diet-Fed Mice

“…GLUT1, which is primarily localized on the cell surface, is the major glucose transporter in the basal state of skeletal muscle. However, GLUT4 is expressed exclusively in skeletal muscle and fat cells, but the Glut4 mRNA level is mostly unchanged in skeletal muscle of non-insulin-dependent diabetes mellitus [ 22 , 23 ]. Additionally, insulin-like signaling via IRS1/2 is essential for the regulation of skeletal muscle growth and metabolism for metabolic homeostasis.…”