Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult polycystic kidney disease (APKD) is a common hereditary disease with renal and extra-renal manifestations. There are at least three genes responsible for this disease. The polycystic kidney disease 1 (PKD1) gene product is a membrane protein involved in cell-cell and cell-matrix interactions and has a widespread tissue distribution. Abnormal membrane fluidity in erythrocytes from APKD patients is due to altered membrane proteins. Membrane fluidity of mononuclear cells is related to whole body insulin sensitivity. Insulin sensitivity might therefore be disturbed in APKD if the erythrocyte membrane abnormality is also present in other cells. Therefore, we investigated insulin sensitivity in 15 APKD patients and 20 normal subjects matched for age and sex. Insulin sensitivity was assessed by a short insulin tolerance test to derive the first-order rate constant for the disappearance of glucose (Kitt) and mononuclear leukocyte membrane fluidity was measured by fluorescence anisotropy. The Kitt value (% mmol.liter-1.min-1) was lower in APKD patients than in normal subjects [median (range) 2.2 (1.5 to 6.3) vs. 4.1 (2.0 to 5.4). P < 0.001]. Fasting plasma insulin concentrations were negatively correlated with the Kitt values (r = -0.66, P < 0.001). Core region anisotropy was significantly lower (higher fluidity) in leukocytes from APKD patients [mean (SEM) 0.164 (0.003) vs. 0.174 (0.001), P < 0.001]. Insulin sensitivity was positively correlated with the fluorescence anisotropy of the core region of leukocyte membranes (r = 0.81, P = 0.0001). In conclusion, APKD patients were insulin resistant and some patients were hyperinsulinemic, which may indicate increased cardiovascular risk. The cellular basis of the insulin resistance may be directly related to the proteins causing the disease or to the general change in membrane properties.
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PMID:Insulin resistance in adult polycystic kidney disease. 926 9

The polycystic kidney disease 1 (PKD1) gene product polycystin has been predicted to be an integral membrane protein involved in cell-cell and cell-matrix interactions. The erythrocyte membrane fluidity in autosomal dominant polycystic kidney disease (ADPKD) patients is increased, and this may be due to a membrane cytoskeletal abnormality. The abnormal erythrocyte sodium-lithium countertransport kinetics in-ADPKD are related to an altered thiol protein in the cytoskeleton. The possibility that a similar thiol protein abnormality causes the increased erythrocyte membrane fluidity in ADPKD was investigated. The membrane fluidity of intact erythrocytes from 12 ADPKD patients and 12 healthy control subjects was assessed from the fluorescence anisotropies of 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-diphenyl-hexatriene (TMA-DPH). The effect on membrane fluidity of N-ethylmaleimide (NEM), cytochalasin D, heating at 48 degrees C for 20 min, or more specifically, liposomes containing antibodies to actin or ankyrin, was determined. In erythrocytes from healthy control subjects, the fluorescence anisotropy of DPH (mean +/- SEM: 0.223 +/- 0.001) was decreased after treatment with NEM (0.200 +/- 0.003, P < 0.001), cytochalasin D (0.206 +/- 0.006, P < 0.001), heating (0.199 +/- 0.002, P < 0.001), and antibodies to actin (0.194 +/- 0.002, P < 0.001) or ankyrin (0.196 +/- 0.002, P < 0.001). The TMA-DPH anisotropy (0.279 +/- 0.001) was also decreased after treatment with NEM (0.264 +/- 0.001, P < 0.001), cytochalasin D (0.264 +/- 0.001, P < 0.001), heating (0.265 +/- 0.001, P < 0.001), and antibodies to actin (0.262 +/- 0.002, P < 0.001) or ankyrin (0.262 +/- 0.002, P < 0.001). NEM had no additional effect on the other treatments, suggesting that its target thiol protein was associated with the cytoskeleton. In untreated erythrocytes from ADPKD patients, fluorescence anisotropies of both DPH and TMA-DPH were reduced, and none of the treatments altered the anisotropy of either DPH or TMA-DPH. In ADPKD, a cytoskeletal thiol protein is abnormal and possibly explains abnormal lipid bilayer properties and transport protein function in erythrocytes in this disease.
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PMID:Lack of function of an N-ethylmaleimide-sensitive thiol protein in erythrocyte membrane of autosomal dominant polycystic kidney disease. 944 80