Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine novel sugar transporter-like proteins have been discovered in the past 5 years. The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11 and GLUT12, have been detected in human skeletal muscle. In the present study, we examined the pattern of expression and localization of the GLUT isoforms 8, 11 and 12 in human skeletal muscle using an immunohistochemical approach. Biopsies of human skeletal muscle from sedentary or trained healthy adults, from fetal muscle (24 weeks of gestation), from obese type-2 diabetic subjects, and from patients suffering from polymyositis or amyotrophic lateral sclerosis (ALS) were studied. GLUT8 and 12 immunoreactivity was below detection level in both developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast, GLUT4 was expressed in all investigated muscle fibres, the pattern of expression of GLUT11 differs from that of GLUT4, suggesting a specialized function for GLUT11 with a regulation independent from that of GLUT4. Obesity, type-2 diabetes, training, conditions of de- and reinnervation (ALS) and regeneration (polymyositis) failed to induce GLUT8 or -12 expression. Likewise, the fibre type-dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed exclusively in slow-twitch muscle fibres and is unaffected by physiological and pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not appear to be of importance in human muscle under physiological and pathophysiological conditions.
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PMID:GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre type-specific pattern. 1470 96

Renal tubular glucose reabsorption is mediated by facilitative glucose transporter (GLUT) proteins and energy-dependent sodium glucose luminal transporters. Glucose transport in the diabetic kidney is upregulated and has been implicated in the pathogenesis of progressive diabetic nephropathy. Hyperglycemia, hypertension, and activation of the renin-angiotensin system are believed important in the development of the disease. The present study examines the renal expression of the facilitative glucose transporters GLUT1 and GLUT12 in rat models of diabetic nephropathy. Sprague-Dawley and transgenic (mRen-2)27 rats received either streptozotocin-induced diabetes or vehicle. GLUT12 expression and localization were determined by immunohistochemistry, immunoblotting, in situ hybridization, and confocal immunofluorescence. GLUT1 immunolabeling was detected on the basolateral membrane throughout the nephron. GLUT12 was localized to the distal tubules and collecting ducts. A significant increase in GLUT12 immunolabeling was measured in Ren-2 controls and Ren-2 diabetic animals compared with Sprague-Dawley controls. GLUT12 expression was higher in Ren-2 diabetic compared with Sprague-Dawley diabetic rats. Long-term diabetes resulted in significant increases in GLUT1 levels in the renal proximal tubules and expression was higher in Ren-2 diabetic than Sprague-Dawley diabetic rats. GLUT12 protein was localized to the cytoplasm and to the apical membrane of human and rat distal tubules and collecting ducts. The apical localization of GLUT12 in the distal tubules and collecting ducts suggests that it could contribute to additional glucose reabsorption in the late nephron. Levels of both GLUT1 and GLUT12 are elevated in animal models of hypertension and diabetic nephropathy.
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PMID:Renal expression and localization of the facilitative glucose transporters GLUT1 and GLUT12 in animal models of hypertension and diabetic nephropathy. 1662 80

Glucose uptake from the bloodstream is the rate-limiting step in whole body glucose utilization, and is regulated by a family of membrane proteins called glucose transporters (GLUTs). Although GLUT4 is the predominant isoform in insulin-sensitive tissues, there is recent evidence that GLUT12 could be a novel second insulin-sensitive GLUT. However, its physiological role in the heart is not elucidated and the regulation of insulin-stimulated myocardial GLUT12 translocation is unknown. In addition, the role of GLUT12 has not been investigated in the diabetic myocardium. Thus, we hypothesized that, as for GLUT4, insulin regulates GLUT12 translocation to the myocardial cell surface, which is impaired during diabetes. Active cell surface GLUT (-4 and -12) content was quantified (before and after insulin stimulation) by a biotinylated photolabeled assay in both intact perfused myocardium and isolated cardiac myocytes of healthy and type 1 diabetic rodents. GLUT localization was confirmed by immunofluorescent confocal microscopy, and total GLUT protein expression was measured by Western blotting. Insulin stimulation increased translocation of GLUT-4, but not -12, in the healthy myocardium. Total GLUT4 content of the heart was decreased during diabetes, while there was no difference in total GLUT12. Active cell surface GLUT12 content was increased in the diabetic myocardium, potentially as a compensatory mechanism for the observed downregulation of GLUT4. Collectively, our data suggest that, in contrast to GLUT4, insulin does not mediate GLUT12 translocation, which may function as a basal GLUT located primarily at the cell surface in the myocardium.
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PMID:GLUT12 functions as a basal and insulin-independent glucose transporter in the heart. 2304 16

Endothelium dysfunction has been understood primarily in terms of abnormal vasomotor function, which plays an important role in the pathogenesis of diabetes and chronic diabetic complications. However, it has not been fully studied that the endothelium may regulate metabolism itself. The response gene to complement 32 (RGC-32) has be considered as an angiogenic inhibitor in the context of endothelial cells. We found that RGC-32 was induced by high fat diet in vivo and by glucose or insulin in endothelial cells, and then we set out to investigate the role of endothelial RGC-32 in metabolism. DNA array analysis and qPCR results showed that glutamine-fructose-6-phosphate aminotransferase [isomerizing] 1 (GFPT1), solute carrier family 2 (facilitated glucose transporter), member 12 (SLC2A12, GLUT12) and glucagon-like peptide 2 receptor (GLP2R) may be among possible glucose metabolism related downstream genes of RGC-32. Additionally, in the mice with endothelial specific over-expressed RGC-32, the disposal of carbohydrate was improved without changing insulin sensitivity when mice were faced with high fat diet challenges. Taken together, our findings suggest that RGC-32 in the endothelial cells regulates glucose metabolism related genes and subsequent helps to maintain the homeostasis of blood glucose.
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PMID:Response gene to complement 32 (RGC-32) in endothelial cells is induced by glucose and helpful to maintain glucose homeostasis. 2535 7

Endothelial cells are routinely exposed to elevated glucose concentrations post-prandially in healthy individuals and permanently in patients with metabolic syndrome and diabetes, and so we assessed their sugar transport capabilities in response to high glucose. In human umbilical vein (HUVEC), saphenous vein, microdermal vessels and aorta, GLUT1 (SLC2A1), GLUT3 (SLC2A3), GLUT6 (SLC2A6), and in microdermal vessels also GLUT12 (SLC2A12), were the main glucose transporters as assessed by mRNA, with no fructose transporters nor SGLT1 (SLC5A1). Uptake of 14C-fructose was negligible. GLUT1 and GLUT3 proteins were detected in all cell types and were responsible for ~60% glucose uptake in HUVEC, where both GLUT1 and GLUT3, but not GLUT6 siRNA knock-down, reduced the transport. Under shear conditions, GLUT1 protein decreased, GLUT3 increased, and 14C-deoxy-glucose uptake was attenuated. In high glucose, lipid storage was increased, cell numbers were lower, 14C-deoxy-glucose uptake decreased owing to attenuated GLUT3 protein and less surface GLUT1, and trans-endothelial transport of glucose increased due to cell layer permeability changes. We conclude that glucose transport by endothelial cells is relatively resistant to effects of elevated glucose. Cells would continue to supply it to the underlying tissues at a rate proportional to the blood glucose concentration, independent of insulin or fructose.
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PMID:Transendothelial glucose transport is not restricted by extracellular hyperglycaemia. 2782 69

GLUT4 is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine whether GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by unilateral synergist ablation. After 5 days, muscle weights and ex vivo [3H]-2-deoxy-d-glucose uptake were assessed. Overload-induced muscle glucose uptake and hypertrophic growth were not impaired in muscle-specific GLUT4 knockout mice, demonstrating that GLUT4 is not necessary for these processes. To assess which transporters mediate overload-induced glucose uptake, chemical inhibitors were used. The facilitative GLUT inhibitor cytochalasin B, but not the sodium-dependent glucose cotransport inhibitor phloridzin, prevented overload-induced uptake demonstrating that GLUTs mediate this effect. To assess which GLUT, hexose competition experiments were performed. Overload-induced [3H]-2-deoxy-d-glucose uptake was not inhibited by d-fructose, demonstrating that the fructose-transporting GLUT2, GLUT5, GLUT8, and GLUT12 do not mediate this effect. To assess additional GLUTs, immunoblots were performed. Overload increased GLUT1, GLUT3, GLUT6, and GLUT10 protein levels twofold to fivefold. Collectively, these results demonstrate that GLUT4 is not necessary for overload-induced muscle glucose uptake or hypertrophic growth and suggest that GLUT1, GLUT3, GLUT6, and/or GLUT10 mediate overload-induced glucose uptake.
Diabetes 2017 06
PMID:GLUT4 Is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle. 2827 80