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

Insulin-receptor binding and tyrosine kinase activity have been studied in brown adipose tissue from lean and obese mice. Brown adipose tissue carries functional insulin receptors comparable with those of conventional insulin target tissues. The alpha-subunit (Mr, 130,000) was labeled with photoreactive insulin; the beta-subunit (Mr, 95,000) was phosphorylated in a cell-free system, and its level of phosphorylation was increased in a dose-dependent manner by insulin. Two types of obese mice, mice rendered obese by gold thioglucose injection (GTG obese) and genetically obese ob/ob mice, were used. Insulin-receptor number was decreased by 60-70% in obese mice, when expressed per milligram of plasma membrane protein or per microgram of glycoprotein, whereas only a 30-40% diminution was observed in skeletal muscle, indicating that insulin receptors from brown adipose tissue are greatly affected by the downregulation process. Insulin-stimulated autophosphorylation of the insulin-receptor beta-subunit was decreased by 60-70% in preparations of obese mice compared with lean mice in direct proportion to the diminished level of insulin-receptor number. Similarly, the ability of receptors to catalyze the phosphorylation of a synthetic substrate (copolymer glutamate-tyrosine) was reduced. These results suggest that the decrease in insulin-receptor number and in associated tyrosine kinase activity could explain the insulin-resistant glucose uptake and the alteration in diet-induced thermogenesis described in obese animals.
Diabetes 1986 Nov
PMID:Brown adipose tissue in lean and obese mice. Insulin-receptor binding and tyrosine kinase activity. 353 Aug 52

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.
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PMID:Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. 354 82

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

Breakdown of the blood-retinal barrier in diabetes may be related to alterations in the retinal pigment epithelial (RPE) cell layer. Morphological studies suggest increased permeability of diabetic RPE plasma membranes, and proliferation and flattening of the RPE basal infoldings have been observed in diabetic animals. In order to determine whether these phenomena are associated with changes in membrane protein or sterol composition, we have used quantitative electron-microscope freeze-fracture and filipin-binding techniques to study the RPE basal membrane in streptozotocin diabetic and 3-O-methyl glucose control rats. Perfusion-fixed retinas were processed for freeze-fracture and filipin-binding analysis. Filipin, a polyene antibiotic, binds specifically to 3-beta-hydroxy-sterols to produce membrane deformations recognizable by freeze-fracture. These analyses revealed an 11% increase in the density of intramembrane particles within the cytoplasmic (P-face) leaflet in diabetic rats as compared with the controls (P less than 0.01, t test). The increase occurred primarily in 6-9-nm particles, while smaller particles were decreased (P less than 0.001, chi-square test). Filipin binding was the same in both groups. These results suggest that alterations in intrinsic membrane proteins may contribute to permeability and surface area changes in the diabetic RPE but that RPE membrane sterols are not affected by diabetes.
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PMID:Quantitative freeze-fracture and filipin-binding study of retinal pigment epithelial-cell basal membranes in diabetic rats. 358 11

This study was undertaken to determine whether diabetes alters the viscoelastic properties of erythrocytes. The oldest and youngest 10% fractions of circulating red cells were separated by centrifugation of freshly drawn blood obtained from ten diabetics with disease of one to 20 years' duration and from an equal number of age- and sex-matched control subjects. Cells from each fraction were suspended in phosphate-buffered saline, and their rheologic behavior was examined in a rheoscope. The elongation of cells, the percentage of cells that tank-treaded in response to shear stress, tank-treading frequency, and the rate of recovery of cell shape upon cessation of shear stress were determined in the oldest and youngest 10% of cells for diabetics as well as for controls. All four parameters were virtually identical for diabetics and controls. Additional aliquots of cells were taken for assessment of nonenzymatic glucosylation of hemoglobin and cell membrane protein. The absence of any measurable difference in rheologic behavior of cells from diabetic and control subjects, despite substantial differences in nonenzymatic glucosylation of hemoglobin and cell membrane proteins, suggests that the magnitude of glucosylation observed in these cellular constituents does not alter the viscoelastic properties of the cells. The implication of these observations is that microvascular complications of diabetes are not attributable to altered deformability of red cells.
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PMID:Microrheologic investigation of erythrocyte deformability in diabetes mellitus. 396 83

In order to determine the fluidity of erythrocyte membrane ghosts the degree of random orientation of excited diphenylhexatriene molecules (anisotropy) was examined in normal and diabetic juveniles. A small but significant enhancement of diphenylhexatriene anisotropy was observed in diabetic erythrocyte membranes when compared with control (0.184 +/- 0.013 versus 0.152 +/- 0.010). This alteration was accompanied by an increase of nonenzymatic glycosylation of membrane proteins and haemoglobin in diabetic subjects (25.7 +/- 2.6 versus 21.1 +/- 2.2 and 7.1 +/- 1.4 versus 4.0 +/- 1.0 respectively). Moreover, elevated plasma glycaemia in diabetes was correlated with an increase in membrane anisotropy in the erythrocyte membranes of diabetic juveniles. Linear relationships were seen between glycosylated hemoglobin and glycosylated membrane proteins (r = 0.767) as well as between glycosylated haemoglobin and membrane anisotropy (r = 0.741). We suggest that membrane protein glycosylation enhancement occurring in diabetes could be one of the reasons of the lowered diabetic erythrocyte membrane fluidity.
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PMID:Nonenzymatic protein glycosylation. I. Lowered erythrocyte membrane fluidity in juvenile diabetes. 409 89

The effects of physical training on beta-adrenergic receptors were evaluated in heart ventricular tissue of diabetic rats. Mild diabetes mellitus was induced in rats with streptozotocin (45 mg/kg, iv). They were then submitted to a progressive 10-week running programme on a treadmill. Binding studies were done at six different concentrations of (-) [3H]dihydroalprenolol (0.5 to 14.4 nM) with ventricular membrane preparations from control (n = 13), sedentary diabetic (n = 9) and trained diabetic rats (n = 10). Direct linear plot analysis of the data revealed that the total number of beta-adrenoceptors was reduced in sedentary diabetic rats as compared to control (2231 +/- 207 vs 2922 +/- 211 fmol/ventricles; P less than 0.05); however, there was no significant change in the receptor density expressed as fmol/mg of membrane protein (40 +/- 3 vs 43 +/- 3; P greater than 0.05). On the other hand, the beta-adrenergic binding sites were decreased in training diabetic rats, either expressed as the total number of receptors (1920 +/- 179 vs 2922 +/- 211; P less than 0.01), or as fmol/mg of membrane protein (30 +/- 3 vs 43 +/- 3; P less than 0.01). There was no significant change in the dissociation constant (KD) of these receptors between groups (KD = 4.08 +/- 0.51, 4.69 +/- 0.93 and 2.88 +/- 0.39 nM respectively for control, sedentary diabetic and diabetic trained animals). The basal epinephrine concentration was significantly increased in trained diabetic rats (102 +/- 21 pg/ml vs 47 +/- 7 for control (P less than 0.05) and vs 49 +/- 9 for sedentary diabetic (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in ventricular beta-adrenergic receptors in trained diabetic rats. 609 14

Fetal tissues exposed to hyperinsulinemia in utero have significantly greater numbers of insulin receptors than do those of controls. We have studied this upregulation phenomenon using crude microsomal membranes from fetal rabbit litters exposed to varying degrees of hyperinsulinemia in diabetic pregnant rabbits. We have observed that insulin binding capacity of membranes increased directly with the severity of maternal diabetes, ranging from 8.5 ng in controls to 44.6 ng insulin/mg membrane protein in offspring of severely diabetic animals and related directly with increasing fetal insulin levels (r = 0.77, P less than 0.005). Lipid analyses of fetal lung membranes showed that reduction of phospholipid to protein ratios occurred in the presence of maternal diabetes. Membrane cholesterol-to-phospholipid ratios were also altered in the presence of maternal diabetes. Significantly, increases in plasma membrane microviscosity were noted in the membranes from diabetic offspring. The data suggest that reduction of membrane fluidity is associated with increases in fetal membrane insulin receptors in severely diabetic pregnancies.
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PMID:Increased fetal insulin receptors and changes in membrane fluidity and lipid composition. 628 63

A protocol has been developed for maintaining isolated rat adipose cells in primary tissue culture. Using this protocol, cells remain fully viable and responsive to insulin for at least 24 h, as assessed by measuring 3-0-methylglucose transport, lipogenesis from [U-14C]glucose, and the incorporation of [35S]methionine into total membrane protein. The acute insulin-induced internalization of its own receptor was then examined by biosynthetically labeling cells in culture with either [35S]methionine or [3H]glucosamine, maximally inducing receptor internalization with a 30-min incubation in the presence of saturating insulin, and preparing plasma and low-density microsomal membrane fractions by differential ultracentrifugation. Receptors were immunoprecipitated with anti-receptor antiserum, and the receptor subunits separated by NaDodSO4-PAGE under reducing conditions and analyzed by autoradiography. When cells not acutely treated with insulin are examined, both the 135K alpha- and 95K beta-receptor subunits are prominently labeled in the plasma membrane fraction, but only faintly labeled in the low-density microsomal membrane fraction. Following the induction of maximal acute receptor internalization, both subunits are decreased by 20-30% in the plasma membrane fraction and concomitantly increased in the low-density microsomal membrane fraction. However, the relative molecular weights and labeling intensities of the two subunits remain constant and correspond to those observed in the biosynthetically labeled human lymphocyte receptor. A minor band of Mr congruent to 190K is also labeled, but its labeling intensity is similar in the two membrane fractions from basal cells and does not change in response to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Jan
PMID:Insulin-induced internalization of the insulin receptor in the isolated rat adipose cell. Detection of both major receptor subunits following their biosynthetic labeling in culture. 636 Jul 64

The effects of insulin-dependent diabetes mellitus on glucose transport activity and on the concentrations of glucose transport systems in the plasma and low density microsomal membranes in adipose cells isolated from streptozotocin-induced diabetic rats have been examined. Glucose transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of glucose transport systems estimated by measuring specific D-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity decreases from 0.19 to 0.12 fmol/cell per min with the induction of diabetes, but remains constant per unit cellular surface area and is accompanied by a constant 6 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. Maximally insulin-stimulated glucose transport activity decreases from 3.16 to 1.05 fmol/cell per min and from 0.26 to 0.12 amol/micrometers 2 per min, and is accompanied by a decrease from 25 to 15 pmol of glucose transport systems/mg of plasma membrane protein. These diminished effects of insulin on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction are paralleled by a 45% decrease in the basal number of glucose transport systems per milligram of membrane protein in the low density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. Thus, the "insulin resistant" glucose transport of the adipose cell in the streptozotocin-induced diabetic rat appears to be the consequence of a depletion of glucose transport systems in the intracellular pool.
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PMID:A possible mechanism of insulin resistance in the rat adipose cell in streptozotocin-induced diabetes mellitus. Depletion of intracellular glucose transport systems. 645 76


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