Prenatal Expression of the GLUT4 Glucose Transporter in the Mouse

Vannucci, Susan J.; Rutherford, Tina M.; Wilkie, Mary Beth; Simpson, Ian A.; Lauder, Jean M.

doi:10.1159/000017451

Cited by 26 publications

(22 citation statements)

References 42 publications

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“…Additionally, higher rates of insulin infusion and higher plasma insulin concentrations might increase production of and/or translocation of other glucose transporter isoforms, including GLUT1, which our previous studies did show was responsive to insulin with increased expression and abundance, and GLUT3, which has been found in fetal skeletal muscle (6,14,29,(33)(34)(35)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 91%

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

Anderson

Thamotharan²,

Kao³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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. Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle. Am J Physiol Regul Integr Comp Physiol 288: R473-R481, 2005. First published November 11, 2004; doi:10.1152/ajpregu.00405.2004.-To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemiceuglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth. insulin signaling; fetal growth; glucose transporter 4 IN ADULT ANIMALS and humans, insulin has primarily a metabolic role to regulate skeletal muscle glucose uptake with less effect on skeletal muscle protein synthesis than in rapidly growing tissues. Although increased serum insulin concentration in the fetal sheep has been shown to increase fetal skeletal muscle glucose uptake, especially at pharmacological doses (17,18,20,21), insulin in the rapidly growing fetus seems to act largely as an anabolic hormone, promoting skeletal muscle protein synthesis and growth. In human fetuses, abnormal insulin concentrations contribute to variations in fetal growth; excessive insulin promotes fetal overgrowth, whereas insufficient insulin leads to fetal growth restriction. Animal studies have produced experimental deficiencies in insulin secretion in fetal lambs, resulting in fetal growth restriction and limited carcass protein accretion (27). Also, it has been shown in the neonatal pig that insulin action to promote s...

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Section: Discussionmentioning

confidence: 91%

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

Anderson

Thamotharan²,

Kao³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We and others have previously shown that Glut4 is also expressed in chondrocytic populated growth centers (27,38,61). Glut4 may be more important in pre-and postnatal bone development than in adult life (60). This may contribute to intrauterine growth retardation, which is associated with insulin resistance (8,9,39).…”

Section: Discussionmentioning

confidence: 97%

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Maor

Vasiliver-Shamis

Hazan-Brill

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Skeletal growth, taking place in the cartilaginous growth plates of long bones, consumes high levels of glucose for both metabolic and anabolic purposes. We previously showed that Glut4 is present in growing bone and is decreased in diabetes. In the present study, we examined the hypothesis that in bone, GLUT4 gene expression and function are regulated via the IGF-I receptor (IGF-IR) and that Glut4 plays an important role in bone growth. Insulin and IGF-I actions on skeletal growth and glucose uptake were determined using mandibular condyle (MC) organ cultures and MC-derived primary cell cultures (MCDC). Chondrogenesis was determined by following proliferation and differentiation activities using immunohistochemical (IHC) analysis of proliferating cell nuclear antigen and type II collagen expression, respectively. Overall condylar growth was assessed morphometrically. GLUT4 mRNA and protein levels were determined using in situ hybridization and IHC, respectively. Glut4 translocation to the cell membrane was assessed using confocal microscopy analysis of GFP-Glut4 fusion-transfected cells and immunogold and electron microscopy on MC sections; glucose uptake was assayed by 2-deoxyglucose (2-DOG) uptake. Both IGF-I and insulin-stimulated glucose uptake in MCDC, with IGF-I being tenfold more potent than insulin. Blockage of IGF-IR abrogated both IGF-I- and insulin-induced chondrogenesis and glucose metabolism. IGF-I, but not insulin, induced Glut4 translocation to the plasma membrane. Additionally, insulin induced both GLUT4 and IGF-IR gene expression and improved condylar growth in insulin receptor knockout mice-derived MC. Moreover, silencing of GLUT4 gene in MCDC culture abolished both IGF-I-induced glucose uptake and chondrocytic proliferation and differentiation. In growing bone, the IGF-IR pathway stimulates Glut4 translocation and enhances glucose uptake. Moreover, intact Glut4 cellular levels and translocation machinery are essential for early skeletal growth.

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“…Recent data have shown that GLUT4 and GLUT8 are expressed in the developing mammalian brain and that their expression is modulated throughout the fetal to adult stages (42)(43)(44)(45). GLUT4 is present in the embryo brain as early as embryonic day 9 (E9) and E14 in rats, and the expression level peaks at E14 and is lower at E19 and remains stable thereafter up to adulthood (42,43).…”

Section: Cellular Features Of Glut4 and Glut8 In The Brainmentioning

confidence: 99%

Translocable Glucose Transporters in the Brain

Alquier

Leloup²,

Lorsignol³

et al. 2006

Diabetes

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The discovery of the brain expression of the translocable glucose transporters, GLUT4 then GLUT8, led to the question of their putative role in the central nervous system, particularly in relation to insulin effect. The anatomical, cellular, and subcellular localization of these transporters has been described in detail. It has been shown that, as in peripheral tissues, these transporters are localized both in an intracellular pool and at the plasma membrane. This is coherent with a translocation phenomenon, but the data reporting the effect of insulin on that property of GLUT4 and GLUT8 remains very controversial. Glucose and insulin have been shown to modulate GLUT4 expression. Based on their anatomical features, different hypotheses have been proposed. Because of the colocalization with the insulin receptors, insulin might regulate glucose uptake in specific brain areas. A role in nutrient sensing has also been proposed, since both insulin and GLUT4 are expressed in gluco-excited neurons of the hypothalamus. Some studies suggest a role for GLUT8 in the endoplasmic reticulum stress. Whereas much has been learned about their cellular features in the central nervous system, many questions remain unanswered concerning their physiological functions. Gene knockout strategy specifically in the brain and even more in specific nuclei or type of cells should provide new clues to the physiological role of both transporters in the central nervous system. Diabetes 55 (Suppl. 2): S131-S138, 2006

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Prenatal Expression of the GLUT4 Glucose Transporter in the Mouse

Cited by 26 publications

References 42 publications

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Translocable Glucose Transporters in the Brain

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