GLUT12 and adipose tissue: Expression, regulation and its relation with obesity in mice

Abstract

Aim:The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. Methods: Uptake studies were performed using radio-labelled sugars; α-methyld-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. Results: GLUT12 is expressed in the peri-nuclear region of mouse adipocytes.Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. Conclusion: We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.

Adipose tissue—more than just fat

“…It was previously shown by Purcell et al that transgenic GLUT12‐overexpressing mice show increased insulin sensitivity mediated by an increased glucose clearance rate in insulin‐responsive tissues . In a recent study Gil‐Iturbe et al describe GLUT12 as a leptin‐, adiponectin‐ and insulin‐responsive receptor that plays a role in the modulation of glucose absorption . In this study the authors investigated the uptake of radiolabelled sugars into cells as well as GLUT12 expression under different levels of leptin and adiponectin and other conditions such as hypoxia in cell culture experiments.…”

“…A number of articles addressing basic mechanisms related to obesity have recently appeared in Acta physiologica. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] One area of clinical relevance for obese patients is the immune system. Duan et al 20 recapitulate the connections between a high-fat diet and diseases.…”

“…24 In a recent study Gil-Iturbe et al describe GLUT12 as a leptin-, adiponectin-and insulin-responsive receptor that plays a role in the modulation of glucose absorption. 8 In this study the authors investigated the uptake of radiolabelled sugars into cells as well as GLUT12 expression under different levels of leptin and adiponectin and other conditions such as hypoxia in cell culture experiments. Interestingly, the same stimuli produce opposite effects on GLUT12 and GLUT4 expression.…”

GLUT12—A promising new target for the treatment of insulin resistance in obesity and type 2 diabetes

“…In this issue of Acta Physiologica, Gil‐Iturbe et al show how activity of the facilitative glucose transporter 12 (GLUT12, SLC2A12) in adipose tissues is regulated by metabolic signals such as insulin, leptin, adiponectin, tumour necrosis factor alpha (TNFα) and hypoxia . Using both in vitro and in vivo approaches, the authors compare the hormonal modulation of GLUT12 expression and activity to that of GLUT4, the main insulin‐sensitive transporter responsible for glucose uptake …”

“…Moreover, overexpression of GLUT12 improves insulin sensitivity and glucose clearance in mice . The work from Gil‐Iturbe et al now shows that in the absence of insulin GLUT12 locates in the perinuclear region of adipose cells . After insulin stimulation, activation of the phosphoinositide 3‐kinase/ protein kinase B (PI3K/AKT) pathway promotes the translocation of GLUT12 transporter molecules to the plasma membrane and increases glucose uptake into the cell.…”