UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of the red blood cell glucose transporter was compared in samples from subjects with and without diabetes. Activity of the glucose transporting protein (GLUT-1) was measured by determining the first order rate constant for uptake of sorbose, a sugar transported by GLUT-1. Red cells were isolated from 13 patients with diabetes and 9 patients without diabetes and were washed free of intracellular glucose. The uptake rate constant was calculated from measurements of sorbose uptake at 0, 1, 2, 5 and 90 minutes at 37 degrees C. The rate constant was significantly decreased in cells isolated from patients with diabetes (0.242 vs 0.303 min-1 in non-diabetic subjects, p < 0.005). The number of GLUT-1 present per mg of membrane protein and clinical parameters such as weight, age, serum cholesterol and urea nitrogen were not significantly different between the groups. The rate constant per pmol of GLUT-1 was significantly decreased in the diabetic subjects. The relationship between diabetes control and the rate constant was not linear and there was no relationship between the calculated intrinsic activity and the HA1c. Because red cell GLUT-1 are not translocated and red cells do not synthesize new proteins, these data suggest that the intrinsic function of the glucose transporter from red cells of patients with diabetes is diminished. This may be due to alterations in the transporter or its membrane environment.
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PMID:Reduction of red cell glucose transporter intrinsic activity in diabetes running. 815 Apr 20

We investigated the tissue-specific developmental expression and localization of GLUT-1 protein in the rat embryo and visceral yolk sac (VYS) during the organogenic periods of normal rats. The expression of GLUT-1 protein was then compared to that of experimental diabetic rats to test whether the diabetic state would affect the regulation of the glucose transporter during the early postimplantation periods (9.5-14.5 days), as we have previously demonstrated that GLUT-1 protein in embryo and VYS was down-regulated in culture with hyperglycemic medium. In the embryo, GLUT-1 protein was highly expressed during the early stages of organogenesis (between 9.5-12.5 days) and declined thereafter, whereas in the VYS, its strong expression was observed at the later stages (from 12.5-14.5 days). Immunohistochemical localization of the GLUT-1 protein in the embryo during the main periods of neurulation (9.5-11.5 days) showed that GLUT-1 immunoreactivity was principally observed in the neuroepithelial cells of the neural tube and also noted in the primitive heart, primitive gut, otic, and optic vesicles. At 12.5 days, GLUT-1 protein started to be expressed in the microvessels at the cranial portions of the neural tube, although its expression in the neuroepithelial cells still remained at the caudal (tail) portions of the neural tube. In the later stages (13.5-14.5 days) after completion of neural tube formation, GLUT-1 protein immunoreactivity substantially decreased in the neuroepithelial cells and was found mainly in the microvessels of the brain vesicles and spinal cord, whereas it continued to be expressed in the heart and eyes. In the VYS, its immunoreactivity was noticeably confined to the endodermal layer, which started as a simple layer and developed wave-like folds in the later stages. The levels of GLUT-1 protein in embryo and VYS from diabetic rats, determined by Western blot analysis, were not down-regulated compared to those in control rats at the different gestational days. Likewise, comparison of GLUT-1 protein immunoreactivity of various tissues in embryo and VYS, focusing on the neural tube, also revealed no significant differences between the two groups. We demonstrated that GLUT-1 protein is abundantly expressed in embryonic tissues and VYS during the early periods of organogenesis. The lack of down-regulation and the continuous abundant expression of the GLUT-1 protein despite the diabetic state in embryo and VYS during the early postimplantation periods may increase delivery of glucose from the VYS into various differentiating embryonic cells, leading to diabetes-induced congenital malformations.
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PMID:Cellular-tissue localization and regulation of the GLUT-1 protein in both the embryo and the visceral yolk sac from normal and experimental diabetic rats during the early postimplantation period. 829 81

Adipocytes play an important role in normal physiology as a major site for systemic energy homeostasis. In disorders such as diabetes, adipocyte function is markedly altered. In this study, we investigated the effect of pioglitazone, a novel antidiabetic agent known to lower plasma glucose in animal models of diabetes mellitus, on cellular differentiation and expression of adipose-specific genes. Treatment of confluent 3T3-F442A preadipocyte cultures for 7 days with pioglitazone (Pio; 1 microM) and insulin (Ins; 0.17 microM) resulted in > 95% cell differentiation into lipid-accumulating adipocytes in comparison with 60-80% cell differentiation by treatment with either agent alone. Analysis of triglyceride accumulation showed increases of triglyceride content over time above untreated preadipocytes by treatment of the cells with Ins, Pio, and especially with Ins + Pio. Basal glucose transport, as measured by cellular uptake of 2-deoxy-D-[14C]glucose, was likewise enhanced in a time-dependent manner by treatment of preadipocytes with Ins, Pio, or Ins + Pio, such that a synergistic effect resulted from the combined treatment with both agents. It was further determined that RNA transcript abundance for genes encoding glucose transporters GLUT-1 and GLUT-4, as well as the adipose-specific genes encoding adipsin and aP2, were increased by the Ins, Pio, or Ins + Pio treatment. Taken together, these findings indicate that pioglitazone is a potent adipogenic agent. By promoting differentiation, this agent may move cells into a state active for glucose uptake, storage, and metabolism.
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PMID:Antidiabetic agent pioglitazone enhances adipocyte differentiation of 3T3-F442A cells. 833 8

Purified immunoglobulin G (IgG) from the serum of patients with insulin-dependent diabetes mellitus (IDDM) of recent onset inhibits high-Km uptake of 3-O-methyl-beta-D-glucose by rat pancreatic islets. To determine if the inhibition is the result of antibodies against GLUT-2, the high-Km glucose transporter of beta cells, we incubated IDDM sera with rat islet cells and with AtT-20ins cells transfected to express GLUT-2. IDDM sera inhibited glucose uptake in islet cells and in GLUT-2-expressing AtT-20ins cells but not in AtT-20ins cells transfected to express the low-Km isoform, GLUT-1. In 24 of 30 (77%) patients with newly diagnosed IDDM, IgG binding as measured by immunofluorescence and flow cytometry of the cells transfected to express GLUT-2 was > 2 standard deviations from the mean of the nondiabetic population; 29 of 31 (96%) of nondiabetic children were negative (P < 0.0001). Increased IgG binding could be removed by absorption with GLUT-2-expressing cells but not with GLUT-1-expressing cells. We conclude that most patients with IDDM of recent onset have autoantibodies to GLUT-2.
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PMID:Autoantibodies to the GLUT-2 glucose transporter of beta cells in insulin-dependent diabetes mellitus of recent onset. 843 87

Vascular disease is a prominent complication of diabetes mellitus, and hyperglycemia has been implicated as a risk factor for the development of these vascular complications. It has previously been suggested that down-regulation of glucose transport in response to hyperglycemia might serve a protective role by decreasing intracellular glucose concentrations. In the present study, regulation of glucose transport by extracellular glucose concentrations was investigated in cultured rat vascular smooth muscle cells (VSMCs). Confluent quiescent VSMCs were exposed to medium containing either normal (5 mmol/L) or elevated (20 mmol/L) extracellular glucose concentrations for 24 hours. VSMCs exposed to elevated extracellular glucose concentrations (with or without serum) for 24 hours exhibited significant decreases in 2-deoxyglucose (2-DG) and D-glucose uptake rates. This decreased glucose transport was associated with a decrease in the Vmax of D-glucose transport without a change in KM. In the absence of serum, a decrease in the quantity of GLUT-1 transport protein at the plasma membrane was noted in cells exposed to elevated extracellular glucose concentrations for 24 hours. Intracellular glucose concentrations were estimated by using two methods, and the results revealed significantly higher intracellular glucose concentrations in the cells exposed to elevated extracellular glucose concentrations for 24 hours. These results suggest that down-regulation of glucose transport in cultured VSMCs exposed to elevated extracellular glucose concentrations for 24 hours does not occur to an extent that normalizes intracellular glucose concentrations. This prolonged increase in intracellular glucose concentrations and the potential associated toxicity may explain the increased incidence of vascular complications in patients with diabetes mellitus.
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PMID:Down-regulation of glucose transport by elevated extracellular glucose concentrations in cultured rat aortic smooth muscle cells does not normalize intracellular glucose concentrations. 862 88

Ethanol consumption has been associated with glucose intolerance and insulin resistance and is suggested to be an independent risk factor in the development of non-insulin-dependent diabetes mellitus. We have investigated the long-term effects of ethanol consumption on insulin-regulated glucose transport in rat adipocytes. Male Wistar rats were fed a high-fat liquid diet containing 35% ethanol (ethanol fed) or a control diet that isocalorically substituted maltose dextrin for ethanol (ad libitum). A third group was pair fed the control diet. Basal rates of 2-deoxyglucose uptake were similar in adipocytes from all three groups. Treatment with insulin increased 2-deoxyglucose uptake in ad libitum- and pair-fed rats but did not stimulate uptake in ethanol-fed rats. Similarly, although okadaic acid increased 2-deoxyglucose uptake in pair-fed rats, it had no effect in ethanol-fed rats. GLUT-1 quantity was greater in pair-fed and ethanol-fed rats compared with ad libitum controls. GLUT-4 was decreased in ethanol-fed compared with pair-fed rats but was not different from ad libitum controls. In ad libitum- and pair-fed rats, insulin increased the translocation of GLUT-4 to the cell surface by 2.0-fold. In contrast, translocation of GLUT-4 was not observed after insulin stimulation of ethanol-fed rats, paralleling the loss of insulin-stimulated glucose uptake. In ethanol-fed rats, GLUT-4 protein quantity was negatively associated with increased Gs alpha protein and isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate production. These data suggest that loss of insulin-stimulated glucose uptake in rat adipocytes after chronic ethanol feeding is at least partially due to decreased movement of GLUT-4 to the cell surface after insulin stimulation.
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PMID:Chronic ethanol feeding in a high-fat diet decreases insulin-stimulated glucose transport in rat adipocytes. 884 41

We tested the hypothesis that diabetes impairs myocardial glucose uptake and pyruvate oxidation under normal conditions and during a dobutamine-induced increase in work. We also tested the hypothesis that an increase in work would result in a decrease in the levels of malonyl CoA, a potent inhibitor of carnitine palmitoyltransferase I (CPT I). Streptozotocin-diabetic micropigs were compared with a nondiabetic control group (n = 8 per group). Triglyceride emulsion, glucose, and somatostatin were infused into the nondiabetic group to create an acute diabetic-like state. In accord with our hypothesis, malonyl CoA decreased significantly with dobutamine in both groups, providing a possible mechanism for increased fatty acid oxidation through relieved inhibition on CPT I. In the absence of dobutamine, glucose uptake and tracer-measured lactate uptake were decreased by 57 and 80%, respectively, in the diabetic group. Dobutamine infusion resulted in similar increases in cardiac contractility, oxygen consumption, and glucose uptake in both groups despite reductions of 50-65% in GLUT-4 and GLUT-1 protein in the diabetic group. Diabetic animals possessed a defect in myocardial pyruvate oxidation, as reflected in increased lactate production, and depressed lactate uptake and pyruvate dehydrogenase activity under control and dobutamine conditions. In conclusion, the major derangement in carbohydrate metabolism in diabetic myocardium was not in glycolysis but, rather, in pyruvate oxidation.
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PMID:Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart during dobutamine-induced work. 899 89

This study determined whether dynamic exercise training of diabetic rats would increase the expression of the GLUT-4 glucose transport protein in prepared cardiac sarcolemmal membranes. Four groups were compared: sedentary control, sedentary diabetic, trained control, and trained diabetic. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained control and diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Sarcolemmal membranes were isolated by using differential centrifugation, and the activity of sarcolemmal K(-)-p-nitrophenylphosphatase (pNPPase; an indicator of Na(+)-K(+)-adenosinetriphosphatase activity) was quantified. Hearts from the sedentary diabetic group exhibited a significant depression of sarcolemmal pNPPase activity. Exercise training did not significantly alter pNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative to control rats. In the trained diabetic animals, sarcolemmal GLUT-4 protein levels were only reduced by 50% relative to control values, whereas GLUT-4 mRNA were returned to control levels. The increase in myocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heart by enhancing myocardial glucose oxidation and cardiac performance.
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PMID:Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. 907 70

This study describes the effects of diabetes on brain growth, cerebral glucose utilization (CGU), and the glucose transporter proteins GLUT-1 and GLUT-3 in the genetically diabetic db/db mouse. Mice were studied at 5 and 10 wk of age and compared with age-matched nondiabetic littermates. At 5 wk, db/db mice were not yet hyperglycemic, but their body weights were 27.5% greater than those of their nondiabetic littermates. By 10 wk, db/db mice were both hyperglycemic (blood glucose values of 39.3 +/- 4.3 vs. 12.1 +/- 2.1 mmol/l for db/db and control, respectively) and obese, with a twofold increase in body weight. Significant reductions in brain weight were observed at 5 wk (15% decrease in brain wet wt), and no further brain growth was observed, such that by 10 wk, brains of db/db mice were 25% smaller than those of control mice; brain wet weight-to-dry weight ratios were slightly reduced. Global rates of CGU, as determined with 2-[14C]deoxyglucose, were significantly reduced in the 10-wk diabetic mice. Levels of brain glucose and brain-to-blood glucose ratios were increased in 5- and 10-wk db/db mice, reflecting adequate glucose delivery to the brain. Blood-brain barrier GLUT-1 levels were unchanged, and mRNA levels were regionally increased. The expression of the neuronal glucose transporter GLUT-3 was not reduced to a significant extent in brains of db/db mice. The results of this study indicate that the db/db mouse has markedly decelerated brain growth accompanied by global reductions in glucose metabolism that are not due to reductions in glucose transport capacity.
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PMID:Glucose utilization and glucose transporter proteins GLUT-1 and GLUT-3 in brains of diabetic (db/db) mice. 912 34

To determine the molecular mechanisms of diabetes-related changes in the expression of GLUT-1 in cerebral tissue, streptozotocin-induced diabetic rats and vehicle injected controls were studied after 4 weeks of diabetes. The GLUT-1 mass in cerebral microvessels was reduced in diabetic rats by approximately 38% (P < 0.01). The GLUT-1 concentration in insulin-treated diabetic group was not significantly different from controls. The GLUT-1 mRNA content of cerebral tissue in diabetic rats (0.064 +/- 0.007) was significantly reduced compared to control rats (0.122 +/- 0.011) or insulin-treated diabetic rats (0.122 +/- 0.015) P < 0.01. The in vitro translation of GLUT-1 mRNA of diabetic rats (0.793 +/- 0.047 arbitrary units) was also significantly lower than that in control rats (1.403 +/- 0.153) P < 0.01 or insulin-treated diabetic rats. (1.124 +/- 0.083) P < 0.01. These changes occurred in asssociation with a reduction in poly (A) tail length of GLUT-1 mRNA which decreased from a control value of 200-350 nt to only 50-100 nt in diabetic rats. Shortening of poly (A) tail of mRNAs is a novel mechanism of diabetes-related changes in the expression of specific genes which are regulated at a translational level.
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PMID:Shortening of poly (A) tail of glucose transporter--one mRNA in experimental diabetes mellitus. 913 78

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