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)

Intrathymic (i.t.) injection of islet cells or whole islets retards development of insulin dependent diabetes mellitus (IDDM) in spontaneous animal models of the disease. Protection of 4-week-old prediabetic NOD/Lt female mice from subsequent IDDM development was specific for the it route of administration since intraperitoneal injection of an equal number of syngeneic islets failed to retard IDDM. The protective effect of i.t. injection of islet cells was compared with the effect of i.t. injection of syngeneic peritoneal exudate cells, NIT-1 cells, bovine serum albumin (BSA), ABBOS peptide, a 52 kDa islet cell membrane protein, various synthetic peptides from human glutamic acid decarboxylase (GAD) and a Coxsackievirus B4-derived peptide with homology to GAD. Interestingly, only a GAD-derived peptide containing sequence homology to Coxsackie-virus B4, and the corresponding Coxsackievirus B4-derived peptide, delayed IDDM onset. To establish the immunological mechanism underlying the reduced IDDM incidence following i.t. injection of islet cells, adoptive transfer of splenic leukocytes into NOD-scid/scid mice was performed. Splenic leukocytes from i.t.-injected non-diabetic females transferred IDDM into NOD-scid/scid recipients, but more slowly than splenocytes from unmanipulated, diabetic (control) donors. Co-transfer of 1:1 mixtures of splenic leukocytes from it islet-injected (and diabetes-free) NOD/Lt females and from untreated NOD/Lt diabetic donors produced IDDM as rapidly as splenocytes from diabetic donors injected alone. Hence, any peripheral suppression generated in i.t.-protected females was not sufficiently strong to prevent IDDM transfer by committed T-effector cells from the diabetic donors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The thymus as a site for evaluating the potency of candidate beta cell autoantigens in NOD mice. 788 41

Complexes made up of the kinases, hexokinase and glycerol kinase, together with the outer mitochondrial membrane voltage-dependent anion channel (VDAC) protein, porin, and the inner mitochondrial membrane protein, the adenine nucleotide translocator, are involved in tumorigenesis, diabetes mellitus, and central nervous system function. Identification of these two mitochondrial membrane proteins, along with an 18 kD protein, as components of the peripheral benzodiazepine receptor, provides independent confirmation of the interaction of porin and the adenine nucleotide translocator to form functional contact sites between the inner and outer mitochondrial membranes. We suggest that these are dynamic structures, with channel conductances altered by the presence of ATP, and that ligand-mediated conformational changes in the porin-adenine nucleotide translocator complexes may be a general mechanism in signal transduction.
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PMID:Microcompartmentation of energy metabolism at the outer mitochondrial membrane: role in diabetes mellitus and other diseases. 807 85

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

RT6 is a T cell membrane protein that has attracted interest because a defect in RT6 expression is associated with susceptibility to autoimmune type I diabetes in DP-BB rats and NOD mice. Using PCR screening of human/rodent somatic cell hybrids and fluorescence in situ hybridization, we have determined that the gene for the human RT6 homologue is located at 11q13, centromeric to the gene for tyrosinase (TYR, albino locus) and telomeric to that for fibroblast growth factor 4 (FGF4). The data suggest that the human RT6 gene constitutes a new linkage group with TYR and the gene for olfactory marker protein (OMP) on 11q, which has a counterpart in mouse chromosome 7. Thus, in the human, the RT6 locus is dissociated from the hemoglobin beta chain locus (HBB) and its neighboring conserved linkage group at 11p15, in contrast to the mouse, in which RT6 shows a tighter linkage to Hbb than to Tyr. The results support the conclusion that there has been considerable intrachromosomal reshuffling of linked genes since the divergence of primates and rodents.
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PMID:Assignment of the human RT6 gene to 11q13 by PCR screening of somatic cell hybrids and in situ hybridization. 828 46

Features of insulin binding to trophoblast plasma membranes were studied in six normal pregnant women (NP), six overt diabetes (ODP) and six poorly controlled glycemic gestational patients (PCDP) i.e. women who did not strictly follow the management of diabetes mellitus during pregnancy. A decreased maximum specific insulin receptor binding per 0.1 mg membrane protein in placenta from PCDP (12%) was found comparing with that from ODP or NP (17.5% and 36.2%, respectively, P < 0.01), The insulin binding in PCDP declined at a faster rate until it reached minimum when studied at a higher temperature (25-37 degrees C). The binding equilibrium was likewise attained faster at this temperature than that at lower temperature of 4 degrees C for all studied groups. The insulin receptor binding in all studied groups was pH dependent. The maximum binding in ODP and PCDP groups was attained at pH 7.8 while for NP maximum binding was at pH 7.4. The competitive binding assay was carried out with 14 concentrations of unlabelled insulin and the half maximal displacement of 125I-insulin was at 8 x 10(-9) M, 6 x 10(-9) M and 4 x 10(-9) M for NP, ODP and PCDP, respectively (P < 0.05) suggesting the differences in the effect of glycemic control on the insulin binding. Furthermore the binding yielded curvilinear Scatchard plots with the apparent affinity of the receptors being affected in the ODP and PCDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Features of insulin receptor interaction in placenta from normal, overt and poorly controlled gestational diabetic patients. 830 91

Numerous alterations in the structure and function of red blood cells and blood platelets in diabetes mellitus result from the process of nonenzymatic glycosylation of proteins. Nonenzymatic attachment of glucose to cell membrane protein amino group, for example, can accompany hypoglycaemia. Chemical modifications of membrane proteins are likely to lead to alterations in the dynamic properties of lipid bilayer and membrane fluidity in diabetic blood cells. Conformational changes of membrane and cytosol proteins glycosylation may underline changes in blood rheology and platelet hypersensitivity in diabetes mellitus.
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PMID:[Role of nonenzymatic glycosylation of proteins in disorders of erythrocytes and blood platelets in diabetes mellitus]. 837 20

Biochemical mechanisms underlying impaired myocardial glucose utilization in diabetes mellitus have not been elucidated. We studied sarcolemmal vesicles (SL) in control, streptozotocin-induced diabetic (D), and insulin-treated diabetic (Tx) rats and found that 3-O-methylglucose transport rates were decreased 53% in D rats and were normalized by insulin therapy. Immunoblot analyses of SL revealed that GLUT4 glucose transporters were decreased 56% in D and were normal in Tx rats. Thus diminished transport rates could be fully explained by reduced numbers of SL GLUT4 with normal functional activity. To determine whether SL GLUT4 were decreased due to tissue depletion or abnormal subcellular distribution, we measured GLUT4 in total membranes (SL plus intracellular fractions). Total GLUT4 (per mg membrane protein or per DNA) was decreased 45-51% in D [half time = 3.5 days after streptozotocin], and these values were restored to normal in Tx rats. Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy. We conclude that, in diabetes, 1) impaired myocardial glucose utilization is the result of a decrease in glucose transport activity, and 2) transport rates are reduced due to pretranslational suppression of GLUT4 gene expression and can be corrected by insulin therapy. GLUT4 depletion could limit glucose availability under conditions of increased workload and anoxia and could cause myocardial dysfunction.
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PMID:Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy. 845 85

The expression of angiotensin (Ang) II receptors, active renin and prorenin in porcine and bovine ovarian follicles and corpora lutea was investigated and compared. In the wall tissue of porcine follicles, the Ang II receptor density was 47 (range 19-97; n = 13) fmol/mg membrane protein. The active renin concentration was 1.32 (0.40-3.43; n = 23) GU/kg wet tissue. These values were about 35-fold and 15-fold lower, respectively, than previously found in bovine follicles. No prorenin could be detected in the porcine follicular wall tissue. Ang II receptors of subtype 2 (AT2 receptors) with a dissociation constant (Kd) of 1.01 (0.64-1.79; n = 8) nmol/l for [Sar1-Ile5-Ile8]-Ang II were demonstrated in the bovine corpus luteum. The receptor density was 22.7 (1.9-93; n = 26) fmol/mg membrane protein, which was about 10-fold higher than in porcine corpora lutea. The active renin concentration was 20.7 (2.2-60.0; n = 26) GU/kg tissue in bovine and 0.40 (0.16-1.09; n = 17) GU/kg tissue in porcine corpora lutea. No prorenin could be detected in corpora lutea from both species. The variation between species in expression of the ovarian renin-angiotensin system indicates the existence of species differences in the physiological role.
Exp Clin Endocrinol Diabetes 1995
PMID:Differences in expression of angiotensin II receptors and renin in porcine and bovine ovaries. 853 63

Islet cell autoantigen (ICA) 512 is a novel autoantigen of insulin-dependent diabetes mellitus (IDDM) which is homologous to receptor-type protein tyrosine phosphatases (++PTPases). We show that ICA 512 is an intrinsic membrane protein of secretory granules expressed in insulin-producing pancreatic beta-cells as well as in virtually all other peptide-secreting endocrine cells and neurons containing neurosecretory granules. ICA 512 is cleaved at its luminal domain and, following exposure at the cell surface, recycles to the Golgi complex region and is sorted into newly formed secretory granules. By immunoprecipitation, anti-ICA 512 autoantibodies were detected in 15/17 (88%) newly diagnosed IDDM patients, but not in 10/10 healthy subjects. These results suggest that tyrosine phosphorylation participates in some aspect of secretory granule function common to all neuroendocrine cells and that a subset of autoantibodies in IDDM is directed against an integral membrane protein of insulin-containing granules.
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PMID:ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. 864 Dec 76

An insulin granule membrane protein-tyrosine phosphatase (PTP) homologue, phogrin, was cloned by expression screening of a rat insulinoma cDNA library. The 3723-base pair cDNA encoded a transmembrane glycoprotein of 1004 amino acids (Mr 111876) that underwent post-translational proteolysis to 60-64-kDa products after a 30-min delay. The kinetics of proteolytic conversion (t1/2 = 45 min) and turnover (t1/2 = 12 h) were consistent with sorting and conversion in a late compartment of the secretory pathway. Studies on the native beta-cell protein suggested that the COOH-terminal PTP domain was on the cytosolic face of the secretory granule. The lumenal segment was comprised of a protease-resistant globular domain of around 25 kDa. Its localization and topology is thus consistent with a transmembrane receptor function related to granule biogenesis, exocytosis, or subsequent membrane recovery, and it should prove to be a useful cell biological marker for the granule membrane. High expression of the mRNA (5.4 kilobases) and protein was evident in islets, pancreatic alpha- and beta-cell tumor lines, brain cells, and other cells of neuroendocrine lineage. It is closely related to the diabetic autoantigen ICA512 (IA-2) (42% identity overall; 80% in the 260-amino acid PTP domain) and thus a potential target of autoimmunity in diabetes mellitus.
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PMID:Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes. 866 34


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