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

Cellular resistance to insulin caused by a reduction in insulin-mediated glucose uptake can be produced in rats by chemically inducing diabetes with streptozotocin and by fasting. Two glucose transporter isoforms are expressed in fat cells: (1) the insulin-responsive species which is found only in fat and muscle, and (2) a species corresponding to the erythrocyte/Hep G2/rat brain transporter. We show here that fat cells isolated from streptozotocin diabetic rats and from fasted rats show a significant (60-80%) decrease in the amount of immunologically detectable insulin-sensitive glucose transporter and no change in the level of the Hep G2/rat brain transporter. Administration of insulin and refeeding, respectively, result in a return of the insulin-sensitive glucose transporter to levels that are normal or slightly above normal. Thus, peripheral tissue insulin resistance could be due to the specific reduction in the amount of insulin-sensitive glucose transporter.
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PMID:Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. 273 28

The blood-brain barrier (BBB) glucose transporter activity in vivo is known to be down-regulated in experimental diabetes mellitus. To determine whether parallel changes in BBB glucose transporter mRNA levels occur in experimental diabetes we isolated brain microvessels, which make up the BBB in vivo, from both control and experimental diabetic rats. Microvessel RNA fractions were isolated by cesium chloride density gradient centrifugation and were applied to 1.1% agarose gels for Northern blotting. The blots were probed with [32P]-labeled cDNAs corresponding to the rat brain glucose transporter and a cDNA to alpha-actin was used to monitor the transcript level of a typical housekeeping gene. The study was repeated three times and, in all cases, the BBB glucose transporter mRNA level was increased in experimental diabetes relative to control rats. These studies suggest that factors associated with experimental diabetes mellitus in rats lead to either an increased transcription or a decreased degradation of brain capillary glucose transporter mRNA.
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PMID:Blood-brain barrier glucose transporter mRNA is increased in experimental diabetes mellitus. 280 7

A DNA sequence polymorphism, revealed by digestion of genomic DNA with the endonuclease Xba1 and hybridisation with a complementary DNA clone for a human glucose transporter, yields two alleles (sizes 6.2 kbp, the X1 allele; or 5.9 kbp, the X2 allele). The genotype frequencies were investigated in three non-insulin-dependent diabetic populations. The frequencies (%) of X1.X1, X1.X2, and X2.X2 were 13, 51, and 36 among 89 North European diabetic subjects, and 8, 38, 54 among their 104 controls (chi 2 test p less than 0.02; G-test p less than 0.02). For 53 South European diabetic patients the frequencies were 19, 50, 31, and for their 41 controls they were 2, 58, 40 (chi 2 test p less than 0.02; G-test p less than 0.01). The corresponding figures were 6, 55, 39 for 45 Japanese patients and 0, 28, 72 for a further 49 controls (chi 2 test p less than 0.01; G-test p less than 0.001). The occurrence of the association of the X1 allele with diabetes in three separate populations suggests that the polymorphic site may be close to a diabetogenic locus on chromosome 1.
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PMID:Association of genetic variant of the glucose transporter with non-insulin-dependent diabetes mellitus. 289 75

The glucose transporter is a membrane glycoprotein that is involved in the uptake of glucose by most, if not all, animal cells. A cloned cDNA that encodes the human protein was used to map the gene to a specific chromosomal region and to identify a DNA polymorphism. The human gene (designated GLUT) was assigned to chromosome 1p31.3----p35 by hybridization of the probe to DNA from a panel of human-mouse somatic cell hybrids containing different human chromosomes and by in situ hybridization to isolated metaphase chromosomes. The most likely location of GLUT is in 1p33. A common two-allele restriction-fragment-length polymorphism was identified with Xba I.
Diabetes 1987 Apr
PMID:Polymorphic human glucose transporter gene (GLUT) is on chromosome 1p31.3----p35. 302 91

Type 2 diabetes is a familial disease and studies of both Caucasian and Japanese families have raised the possibility that a major susceptibility gene is involved. The majority of patients have both beta cell dysfunction and impaired insulin sensitivity but studies of relatives of Type 2 diabetic patients suggest that beta cell dysfunction is an early feature of the disease. Impaired insulin sensitivity, from acromegaly, Cushing's disease or steroid therapy, induces diabetes only in a small proportion of the population, and they may be those who have an inherited cell defect. We postulate that a single beta cell defect gene, on its own, may be insufficient to cause overt diabetes and would lead to life-long glucose intolerance unless associated with other defects such as impaired insulin sensitivity. The nature of such a postulated beta cell defect is uncertain. Whilst it has been reported to be specific to glucose, and not to non-glucose stimuli, this feature may be secondary to hyperglycaemia. The occurrence of islet amyloid in 70-90% of Type 2 diabetic patients, and rarely in the normal population, raises the possibility that amyloid deposition causing disruption of the islet is a factor which might affect beta cell function. Amyloid formation may be a primary abnormality or could be secondary to beta cell dysfunction induced by hyperglycaemia. A major susceptibility gene might predispose a proportion, perhaps 10-15%, of a Caucasian population towards diabetes. The subsequent development of diabetes in a particular patient is likely to depend on many factors including other genetic factors, a sedentary life style and obesity. In different populations different genetic influences may operate, including abnormalities of insulin receptor genes and glucose transporter genes, which may allow a beta cell abnormality to become expressed clinically.
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PMID:Pathogenesis of NIDDM--a disease of deficient insulin secretion. 307 95

The effects of insulin therapy in streptozotocin diabetic rats on the glucose transport response to insulin in adipose cells have been examined. At sequential intervals during subcutaneous insulin infusion, isolated cells were prepared and incubated with or without insulin, and 3-O-methylglucose transport was measured. Insulin treatment not only reversed the insulin-resistant glucose transport associated with diabetes, but resulted in a progressive hyperresponsiveness, peaking with a 3-fold overshoot at 7-8 days (12.1 +/- 0.3 versus 3.4 +/- 0.1 fmol/cell/min, mean +/- S.E.) and remaining elevated for more than 3 weeks. During the peak overshoot, glucose transporters in subcellular membrane fractions were assessed by cytochalasin B binding. Insulin therapy restored glucose transporter concentration in the plasma membranes of insulin-stimulated cells from a 40% depleted level previously reported in the diabetic state to approximately 35% greater than control (38 +/- 4 versus 28 +/- 2 pmol/mg of membrane protein). Glucose transporter concentration in the low-density microsomes from basal cells was also restored from an approximately 45% depleted level back to normal (50 +/- 4 versus 50 +/- 6 pmol/mg of membrane protein), whereas total intracellular glucose transporters were further increased due to an approximately 2-fold increase in low-density microsomal membrane protein. However, these increases remained markedly less than the enhancement of insulin-stimulated glucose transport activity in the intact cell. Thus, insulin treatment of diabetic rats produces a marked and sustained hyperresponsive insulin-stimulated glucose transport activity in the adipose cell with little more than a restoration to the non-diabetic control level of glucose transporter translocation. Because this enhanced glucose transport activity occurs through an increase in Vmax, insulin therapy appears to be associated with a marked increase in glucose transporter intrinsic activity.
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PMID:Mechanism for markedly hyperresponsive insulin-stimulated glucose transport activity in adipose cells from insulin-treated streptozotocin diabetic rats. Evidence for increased glucose transporter intrinsic activity. 354 15

Isolated cardiac myocytes from control and insulin treated diabetic BB rats were used to study cellular alterations related to partly controlled diabetes. Scatchard analysis of equilibrium binding data showed an unaltered affinity and number of insulin receptors in cardiocytes from both groups of animals. Moreover, insulin internalization was found to be identical under these conditions. Insulin action was determined by measuring the effect of the hormone on initial velocities of 3-0-methylglucose influx. Basal activity of the glucose transporter and maximal transport stimulation by insulin remained unaffected. In contrast, the sensitivity of the carrier towards stimulation by insulin was markedly reduced in cardiocytes from diabetic rats with a half-maximal action occurring at an insulin concentration of 3 X 10(-10) mol/l and 9 X 10(-9) mol/l in control and diabetic animals, respectively. The onset of insulin action was much slower in cells from diabetic BB rats exhibiting an increase in the coupling time by 400% from 5 to 20 min, respectively. The data suggest an association of partly controlled diabetes with myocardial alterations located at the postreceptor level.
Diabetes Res 1987 Feb
PMID:Insulin binding and action in isolated cardiocytes from spontaneously diabetic BB rats. 355 55

In this article we have described the hypothesis that insulin stimulates glucose transport through glucose transporter translocation from an intracellular pool to the plasma membrane. In addition, we have shown that changes in the numbers and subcellular distributions of glucose transporters correlate with alterations in insulin-stimulated glucose transport activity in several experimental models of insulin resistance and hyperresponsiveness. However, in experiments with counterregulatory hormones and with hyperresponsive states induced by nutritional repletion following deprivation, changes in insulin responsiveness cannot be fully explained by such alterations in the numbers and/or subcellular distribution of glucose transporters. Thus, evidence has been presented for changes in glucose transporter intrinsic activity that both inhibit and augment insulin-stimulated glucose transport rates. Finally, we have discussed data suggesting that the translocation process is applicable to human tissue and that significant changes in adipose cell glucose transport activity have been correlated with total glucose disposal in various metabolic states in humans. Determining the physiologic factors involved in modulating these events at the cellular level is an important area for further investigation.
Diabetes Metab Rev 1985
PMID:Subcellular translocation of glucose transporters: role in insulin action and its perturbation in altered metabolic states. 391 54

When rats with streptozotocin (STZ)-induced diabetes were given a daily intraperitoneal (i.p.) injection of VOSO4 (+4 oxidation state of vanadium), their serum glucose dropped from hyperglycemic level to normal level within 2d and serum free fatty acid (FFA) level also dropped to normal level. Vanadium was incorporated in most organs as well as in the adipose tissues, as detected by neutron activation analysis (NAA). The mechanism for the insulin-like action vanadium in terms of FFA release from isolated rat adipocytes was investigated: (1) Vanadyl (IV) and vanadic (III) ions normalize the FFA release in the adipocytes treated with epinephrine; (2) vanadate (V) ion treated with ascorbic acid, cysteine or glucose is effective in normalizing the FFA release but vanadate ion alone has no effect on FFA release; (3) vanadyl ion is incorporated into the adipocytes, while vanadate ion is not, as indicated by ESR spectroscopy; and (4) vanadyl ion can act on the glucose transporter, as indicated by experiments using cytochalasin B which is an inhibitor of this transporter. From these results, the normalization of both serum glucose and FFA levels by vanadyl ion was concluded to be due to the incorporation of vanadyl ion into the adipocytes, in which the metal ion acts on the glucose transporter and induces both the promotion of glucose uptake and the decrease of FFA release form peripheral adipocytes. The vanadyl state was suggested to be a possible pharmacologically active form of vanadium allowing the insulin-like action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism on insulin-like action of vanadyl sulfate: studies on interaction between rat adipocytes and vanadium compounds. 749 89

Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels. The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble insulin for 24 h the fasting plasma glucose concentration decreased from 20.8 +/- 2.3 (SD) to 8.7 +/- 2.3 mmol 1-1, whereas the fasting serum insulin level increased from 0.06 +/- 0.02 to 0.17 +/- 0.09 nmol 1-1. However, despite a 2.8-fold increase in serum insulin levels and more than a halving of the plasma glucose concentration for at least 15 h no significant alterations occurred in the amount of GLUT4 protein (0.138 +/- 0.056, poor control vs 0.113 +/- 0.026 arb. units, improved control, p = 0.16) or GLUT4 mRNA (96432 +/- 44985, poor control vs 81395 +/- 25461 arb. units, improved control, p = 0.54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients.
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PMID:The effect of intensive insulin therapy on the insulin-regulatable glucose transporter (GLUT4) expression in skeletal muscle in type 1 diabetes. 750 14


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