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)

The lectin-horseradish peroxidase conjugate of GSA I-B4 (Griffonia simplicifolia isolectin) has some binding affinity with capillary walls in sections of the major salivary glands from normal rats. After inducing diabetes with streptozotocin a conspicuous increase in the staining intensity with GSA I-B4 was already evident in parotid capillaries at 3 weeks and this increase persisted at 3 and 6 months. In submandibular capillaries, however, an increased uptake of GSA I-B4 was evident only at 6 months after inducing diabetes. The reasons for these different time scales in the two glands are not known but the increased uptake of GSA I-B4, which is due to an increase in carbohydrate-containing sites with available terminal alpha-D-galactose, is considered to reflect a pathological change.
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PMID:Changes in the lectin-binding of capillaries in rat salivary glands after streptozotocin-induced diabetes. 141 25

Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D-glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat.
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PMID:Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats. 143 91

Aldose reductase (AR), a major enzyme in the polyol pathway, is thought to be responsible for accumulation of polyols in lenses exposed to high doses of galactose or glucose, and it may be linked to some of the complications found in diabetes. In this report we examined the level of expression of AR mRNA in lens epithelia undergoing development of galactose cataracts in vivo. The AR mRNA was quantitated by Northern blot hybridization with a [35S]-RNA transcript from a previously described AR cDNA clone. This was done on normal lens epithelia and on epithelia from lens of rats fed a diet of Purina Chow containing 50% galactose for periods of from 6 hr to 20 days. We found AR mRNA to elevate to about 5-fold the control levels by 12-24 hr on galactose, then decrease to the control levels by day 4. The increase in AR mRNA appears to be transitory. The high abundance in AR mRNA by 24 hr on galactose was confirmed by in situ hybridization. At later periods, from 8 to 20 days on galactose, a slow increase in AR mRNA took effect, as we have previously reported. Changes in the levels of galactose and dulcitol between 0 and 96 hr were also quantitated by gas chromatography, showing that there was a significant increase in both galactose and dulcitol occurring throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient elevation of aldose reductase mRNA in lens of rats developing galactose cataracts. 143 62

Hypothalamic noradrenergic neuronal activity (NNA) and hepatic glucose output are stimulated by stress. The aim of the present investigation was to examine whether the blockade of noradrenergic responses to stress might suppress the associated hyperglycemia. Mass spectrometry was used for analysis of norepinephrine (NE) and its neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) in rat hypothalamus, and the ratio DHPG/NE was used as an index of NNA. Treatment of rats with 2-deoxy-D-glucose (500 mg/kg ip, -30 min), yohimbine (10 mg/kg ip, -20 min), or neostigmine (2 micrograms icv, -60 min) increased both NNA and serum glucose (P < 0.05). When rats were additionally pretreated with pentobarbital (60 mg/kg ip; -60 min), the NNA responses were blocked (P < 0.01). At the same time the hyperglycemic responses were also inhibited (P < 0.01). In rats that had reduced NNA due to 7 days "gentling," serum glucose levels were also significantly reduced (P < 0.001) compared with naive controls. The data demonstrate that inhibition of central noradrenergic activity is also associated with an inhibition of hyperglycemia, raising the concept that therapies aimed at reducing central NNA may have a role in the management of diseases with excessive hepatic glucose output such as non-insulin-dependent diabetes mellitus.
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PMID:Suppression of central noradrenergic neuronal activity inhibits hyperglycemia. 144 13

Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH-dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions.
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PMID:Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney. 144 70

Expression of GLUTs in rat peripheral nerve was first studied at the mRNA level with Northern transfer analysis with cDNAs specific for GLUT1, GLUT2, GLUT3, and GLUT4. GLUT1 mRNA was the only GLUT mRNA detectable in rat sciatic nerve. In situ hybridization localized this mRNA to the perineurium and to some endo- and epineurial capillaries. Indirect immunofluorescence stainings demonstrated that GLUT1 protein epitopes were concentrated primarily in the perineurium and endoneurial capillaries. Also, some Schwann cells, a few epineurial capillaries, and medium-sized blood vessels showed a faintly positive immunoreaction. All cell types present in primary cultures initiated from rat sciatic nerve (perineurial cells, Schwann cells, and fibroblasts) expressed GLUT1 protein in vitro. Thus, Schwann cells, which expressed GLUT1 only occasionally at a low level in vivo, have the potential to express GLUT1 at a markedly higher level under cell culture conditions. Incubation of the cultures in 25 mM D-glucose for 7 days caused a 39% reduction in the amount of immunodetectable GLUT1 protein, and a marked (34%) decrease of GLUT1 mRNA compared with cultures incubated in 5.5 mM D-glucose. Interestingly, the reduction of [3H]-2-DG uptake in the same cultures exceeded 70%, suggesting that the reduced amount of GLUT1 protein alone did not explain the marked reduction in glucose uptake in these cultures. Immunostaining of the cell cultures suggested that perineurial cells were the main target for the glucose-induced decrease of GLUT1 protein.
Diabetes 1992 Dec
PMID:Glucose transporters of rat peripheral nerve. Differential expression of GLUT1 gene by Schwann cells and perineural cells in vivo and in vitro. 144

Both a high level of D-glucose in the medium and serum from a diabetic rat can induce neural-tube fusion defects and growth retardation in cultured mouse and rat embryos. To test our hypothesis that a deficiency of PGs may be involved in the mechanism of hyperglycemia- and diabetic serum-induced teratogenesis and growth retardation, we added PGE2 to the medium of a whole mouse embryo culture containing either normal rat serum and 52.7 mM D-glucose (hyperglycemic) or diabetic rat serum and 22.2 mM D-glucose (diabetic). After a 24-h culture, 94% of hyperglycemic embryos and 81% of diabetic embryos had neural-tube fusion defects; in addition, the number of somites, the morphological score, and the protein content of the embryos were significantly lower than those of controls. Supplementing the medium with PGE2 at concentrations of 0.028-28.4 nM (hyperglycemic) or 28.4 nM (diabetic) significantly reduced the incidence of neural-tube defects and increased the number of somites, the morphological score, and the protein content. These results strongly support the hypothesis that the teratogenicity of diabetic serum, as well as the teratogenic action of hyperglycemic culture, are mediated through a deficiency of PGs.
Diabetes 1992 Dec
PMID:PGE2 prevents anomalies induced by hyperglycemia or diabetic serum in mouse embryos. 144 6

To obtain information on the regulation of glucose transport across the basolateral membrane (BLM) of intestinal epithelial cells, we measured the number of [3H]cytochalasin B binding sites and the level of liver-type glucose transporter (GLUT2) protein in the BLM in the jejunum of rats (i) with diabetes (ii) given a high-carbohydrate diet or (iii) with experimental hyperglycemia (12 h infusion of a high-glucose solution). A glucose uptake and the number of D-glucose inhibitable [3H]cytochalasin B binding sites in BLM vesicles were significantly increased in all three conditions. Western blot analysis showed that the amount of GLUT2 protein in BLM vesicles was increased in rats with diabetes and those given a high-carbohydrate diet, but not in those with experimental hyperglycemia. These results suggest that there is a mechanism for rapid regulation of glucose transport in the BLM that does not depend on change in the amount of GLUT2.
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PMID:Role of liver-type glucose transporter (GLUT2) in transport across the basolateral membrane in rat jejunum. 146 87

Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia. 148 48

Contractile properties of left ventricular papillary muscles and atria from streptozotocin-diabetic and from non-diabetic rats fed a 40% galactose diet were measured in vitro. There was a characteristic slowing of twitch responses for both tissues and both treatments (P < 0.05). Time to peak contraction was prolonged by 18-33% and maximum rate of contraction was reduced by 10-17%. Relaxation was also affected, with a 13-37% increase in half-relaxation time and a 7-25% reduction in the maximum rate of relaxation. There were treatment differences between papillary muscles and left atrium, diabetes having a more marked effect on the former, whereas galactosaemia caused more pronounced changes in the latter. The resting beat rate of the right atrium was 22% reduced in diabetic and galactosaemic rats (P < 0.01). When maximally stimulated with isoprenaline, beat rate did not rise to the level of stimulated controls (P < 0.01). Papillary muscle speed-related contractile properties also showed a reduced response to isoprenaline in diabetic and galactosaemic groups compared to normal controls. The greatest deficit was found for maximum rate of relaxation where responsiveness was 41 and 34% less for diabetic and galactosaemic groups respectively (P < 0.01). Polyol pathway metabolites in diabetic ventricles were increased 8-fold. In galactosaemic rats galactitol accumulation led to a 530-fold increase in polyols. The data suggest that polyol pathway activity may be an important factor in the aetiology of contractile and chronotropic changes in diabetic and galactosaemic cardiomyopathy.
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PMID:Polyol pathway-mediated changes in cardiac muscle contractile properties: studies in streptozotocin-diabetic and galactose-fed rats. 148 41


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