Insulin-Stimulated Translocation of Glucose Transporter (GLUT) 12 Parallels That of GLUT4 in Normal Muscle

Stuart, Charles Alexander; Howell, Mary E. A.; Zhang, Yi; Yin, Deling

doi:10.1210/jc.2009-0162

Cited by 95 publications

(96 citation statements)

References 23 publications

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“…Phosphoinositide 3-kinase (PI3K) activity in the lysates was evaluated using a PI3K ELISA kit (K1000; Echelon Biosciences, Salt Lake City, UT, USA). The plasma membrane of the muscle was obtained as in Stuart et al [15] and checked by cadherin.…”

Section: Methodsmentioning

confidence: 99%

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

Osanai

Tanaka

Magota³

et al. 2011

Diabetologia

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Aims/hypothesis Despite advances in pharmacological treatments, diabetes with hypertension continues to be a major public health problem with high morbidity and mortality rates. We recently identified a circulating peptide coupling factor 6 (CF6), which binds to the plasma membrane ATP synthase (ecto-F 1 F o complex), resulting in intracellular acidosis. We investigated whether overexpression of CF6 contributes to diabetes and hypertension by intracellular acidosis. Methods Transgenic mice overexpressing CF6 (also known as ATP5J) were generated, and physiological, biochemical and molecular biology studies were performed. Results CF6 overexpression elicited a sustained decrease in intracellular pH in tissues (aorta, kidney, skeletal muscle and liver, with the exception of adipose tissue) that express its receptor, the β-subunit of ecto-F 1 F o complex. Consistent with the receptor distribution, phospho-insulin receptor β, phosphoinositide 3-kinase activity and the phospho-Akt1: total Akt1 ratio were all decreased in the skeletal muscle and the liver in transgenic compared with wild-type mice, resulting in a decrease of plasma membrane-bound GLUT4 and an increase in hepatic glucose production. Under a high-sucrose diet, transgenic mice had insulin resistance and mild glucose intolerance; under a high-salt diet, they had elevated blood pressure with increased renal RASrelated C3 botulinum substrate 1 (RAC1)-GTP, which is an activator of mineralocorticoid receptor. Conclusions/interpretation Through its action on the β-subunit of ecto-F 1 F o complex, which results in intracellular acidosis, CF6 plays a crucial role in the development of insulin resistance and hypertension. This finding might advance our understanding of the mechanisms underlying diabetes and hypertension, possibly also providing a novel therapeutic target against cardiovascular disease.

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Section: Methodsmentioning

confidence: 99%

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

Osanai

Tanaka

Magota³

et al. 2011

Diabetologia

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“…In the blastocyst-stage embryo GLUT8 translocates to the cell surface in response to insulin and mediates insulin stimulated glucose uptake [83]. Additionally, recent data suggests that GLUT12 may also function as an insulin sensitive glucose transporter [84,85]. It is unknown if GLUT8 or GLUT12 function in the oocyte or cumulus cells.…”

Section: Glucosementioning

confidence: 99%

The impact of obesity on egg quality

Purcell

Moley

2011

J Assist Reprod Genet

132

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Obesity in women is a concern in many countries. This causes numerous health issues; however, this review focuses on the impact of obesity on women's reproduction, and in particular the oocyte. Data from infertility clinics and experimental animal models that address the effects of obesity are presented. Bidirectional communication and metabolic support from the surrounding cumulus cells are critical for oocyte development, and the impact of obesity on these cells is also addressed. Both oocyte maturation and metabolism are impaired due to obesity, negatively impacting further development. In addition to reproductive hormones, obesity induced elevations in insulin, glucose, or free fatty acids, and changes in adipokines appear to impact the developmental competence of the oocyte. The data indicate that any one of these hormones or metabolites can impair oocyte developmental competence in vivo, and the combination of all of these factors and their interactions are the subject of ongoing investigations.

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“…In another study, it has been shown a protein expression ratio for GLUT4: GLU12 of 8:1, representing for GLUT12 around 12 % of the potentially insulin translocable GLUT. Moreover, activation of PI3-K was involved in GLUT12 translocation, as has been described for GLUT4 [32].…”

Section: Physiological Rolementioning

confidence: 52%

“…This physiological function was demonstrated in normal human skeletal muscle, where it was described that GLUT12 is translocated to the plasma membrane together with GLUT4 in response to insulin [32]. This fact was recently confirmed in a GLUT12 over-expressing mice, where the whole body insulin sensitivity and the glucose clearance rate in insulin sensitive tissues was higher than in control mice [26].…”

Section: Physiological Rolementioning

confidence: 68%

“…During the past years, research has focused on the study of GLUT12 role as a secondary insulin sensitive transporter [26,32] and its role on impaired insulin signalling pathologies [15,38,39]. Its expression in some tumour tissues has been described [5,29,35] and recently it has been proposed as one of the key proteins in the glucose supply to malignant cells [48] (Figure 5).…”

Section: Summary and Future Directionsmentioning

confidence: 99%

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The facilitative glucose transporter GLUT12: what do we know and what would we like to know?

et al. 2012

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Human GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4.Glucose has been described as its main substrate, but it also can transport other sugars. In humans, GLUT12 protein is expressed mainly in insulin sensitive tissues. Functional analysis has showed that GLUT12 transports sugars down its concentration gradient, but it can also work as a proton-coupled symporter. Studies from our laboratory, performed in Xenopus laevis oocytes expressing GLUT12, show that glucose uptake increases in the presence of Na + and induces inward current. These findings suggest a transport mechanism never described for other GLUTs, which would indicate a distinct functional role for GLUT12. In relation with its physiological and pathophysiological function, GLUT12 has been mainly studied due to its role as a secondary insulin-sensitive glucose transporter and its possible implication in impaired insulin signalling pathologies. Its expression in some tumour tissues has been described and recently, it has been proposed as one of the key proteins in the glucose supply to malignant cells. Overall, even though a lot of information about GLUT12 has been released during the last years, its functional characteristics, physiological role or implication in the development of some diseases is still unclear. Therefore, this review of the literature can help to address further investigations needed to elucidate these issues that, in our view, are of great interest mainly due to the direct GLUT12 relation with cancer and probably with diabetes development.

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Insulin-Stimulated Translocation of Glucose Transporter (GLUT) 12 Parallels That of GLUT4 in Normal Muscle

Cited by 95 publications

References 23 publications

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

The impact of obesity on egg quality

The facilitative glucose transporter GLUT12: what do we know and what would we like to know?

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