GLUT12 expression and regulation in murine small intestine and human Caco‐2 cells
Journal of Cellular Physiology
Published online on October 23, 2018
Abstract
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- "\nAbstract\nGLUT12 was cloned from the mammary cancer cell line MCF‐7, but its
physiological role still needs to be elucidated. To gain more knowledge of GLUT12
function in the intestine, we investigated GLUT12 subcellular localization in the
small intestine and its regulation by sugars, hormones, and intracellular mediators
in Caco‐2 cells and mice. Immunohistochemical methods were used to determine GLUT12
subcellular localization in human and murine small intestine. Brush border membrane
vesicles were isolated for western blot analyses. Functional studies were performed
in Caco‐2 cells by measuring α‐methyl‐d‐glucose (αMG) uptake in the absence of sodium.
GLUT12 is located in the apical cytoplasm, below the brush border membrane, and
in the perinuclear region of murine and human enterocytes. In Caco‐2 cells, GLUT12
translocation to the apical membrane and α‐methyl‐\nd‐glucose uptake by the transporter
are stimulated by protons, glucose, insulin, tumor necrosis factor‐α (TNF‐α), protein
kinase C, and AMP‐activated protein kinase. In contrast, hypoxia decreases GLUT12
expression in the apical membrane. Upregulation of \nTNF‐α and hypoxia‐inducible
factor‐1α (\nHIF‐1α) genes is found in the jejunal mucosa of diet‐induced obese
mice. In these animals, GLUT12 expression in the brush border membrane is slightly
decreased compared with lean animals. Moreover, an intraperitoneal injection of
insulin does not induce GLUT12 translocation to the membrane, as it occurs in lean
animals. GLUT12 rapid translocation to the enterocytes’ apical membrane in response
to glucose and insulin could be related to GLUT12 participation in sugar absorption
during postprandial periods. In obesity, in which insulin sensitivity is reduced,
the contribution of GLUT12 to sugar absorption is affected."
- Journal of Cellular Physiology, EarlyView.