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)

Glycation of basement membrane collagen IV has been implicated as a major pathogenetic process leading to diabetic microvascular complications. To evaluate the relevance of carbohydrate-induced modifications on collagen IV in diabetic nephropathy, we isolated the cross-linking domains 7S and NC1 from the glomerular basement membrane (GBM) of patients with diabetes mellitus. Modifications characteristic for glycated proteins were identified when the domains from diabetic kidney were compared with the same domains from human placenta as an unmodified control. In both domains a marked formation of inter-and intramolecular cross links could be demonstrated by SDS-PAGE. Furthermore circular dichroism studies showed a decrease in helicity of the 7S domain from human diabetic kidneys of 13%, indicating denaturation already at room temperature. Thermal transition profiles, showing a shift of the denaturation temperature towards a lower temperature, with loss of a distinct second melting point, confirmed this observation. Our data provide further evidence for a possible role of protein-modification by glycoxidative reactions in the onset of diabetic nephropathy in vivo.
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PMID:Biochemical and biophysical alterations of the 7S and NC1 domain of collagen IV from human diabetic kidneys. 975 26

Chard (Beta vulgaris L. var. cicla) is one of the plants used as hypoglycaemic agent by diabetics in Turkey and it has been reported to reduce blood glucose. The purpose of this study was to investigate the effect of feeding chard on diabetes induced impairments in rat skins. Uncontrolled induced diabetes caused significant increases in nonenzymatic glycosylation of skin proteins, lipid peroxidation and blood glucose. Administration of chard extract inhibited these effects except the increase in lipid peroxidation. SDS-polyacrylamide gel electrophoresis revealed no significant differences in any protein bands between any of the groups. The data indicate that the use of chard may be effective in preventing or at least retarding the development of some diabetic complications.
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PMID:The effect of chard (Beta vulgaris L. var. cicla) on the skin of streptozotocin induced diabetic rats. 977 Feb 12

The agouti-related protein gene (Agrp) is a novel gene implicated in the control of feeding behavior. The hypothalamic expression of Agrp is regulated by leptin, and overexpression of Agrp in transgenic animals results in obesity and diabetes. By analogy with the known actions of agouti, these data suggest a role for the Agrp gene product in the regulation of melanocortin receptors expressed in the central nervous system. The availability of recombinant, highly purified protein is required to fully address this potential interaction. A nearly full-length form of AGRP (MKd5-AGRP) was expressed in the cytosolic or soluble fraction of Escherichia coli and appeared as large intermolecular disulfide-bonded aggregates. Following oxidation, refolding, and purification, this protein was soluble, and eluted as a single symmetric peak on RP-HPLC. Circular dichroism studies indicated that the purified protein contains primarily random coil and beta-sheet secondary structure. Sedimentation velocity studies at neutral pH demonstrated that MKd5-AGRP is monomeric at low micromolar concentrations. Mobility shifts observed using SDS-PAGE under reducing and nonreducing conditions for bacterially expressed and mammalian expressed AGRP were identical, an indication of a similar disulfide structure. The purification to homogeneity of a second, truncated form of AGRP (Md65-AGRP) which was expressed in the insoluble or inclusion body fraction is also described. Both forms act as competitive antagonists of alpha-melanocyte stimulating hormone (alpha-MSH) at melanocortin-3 (MC-3) and melanocortin-4 receptors (MC-4). The demonstration that AGRP is an endogenous antagonist with respect to these receptors is a unique mechanism within the central nervous system, and has important implications in the control of feeding.
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PMID:Biochemical, biophysical, and pharmacological characterization of bacterially expressed human agouti-related protein. 981 97

HLA-DQ alleles are closely associated with susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM) but the immunologic mechanisms involved are not understood. Structural studies of the IDDM-susceptible allele, HLA-DQA1*0301/DQB1*0302, have classified it as a relatively unstable dimer, particularly at neutral pH. This is reminiscent of studies in the nonobese diabetic mouse, in which I-A(g7) is relatively unstable, in contrast to other murine I-A alleles, suggesting a correlation between unstable MHC class II molecules and IDDM susceptibility. We have addressed this question by analysis of dimer stability patterns among various HLA-DQ molecules. In EBV-transformed B-lymphoblastoid cell lines and PBL, the protein encoded by the IDDM-protective allele HLA-DQA1*0102/DQB1*0602 was the most SDS stable when compared with other HLA-DQ molecules, including HLA-DQA1*0102/DQB1*0604, a closely related allele that is not associated with protection from IDDM. Expression of six different HLA-DQ allelic proteins and three different HLA-DR allelic proteins in the bare lymphocyte syndrome cell line, BLS-1, revealed that HLA-DQA1*0102/DQB1*0602 is SDS stable even in the absence of HLA-DM, while other HLA class II molecules are not. These results suggest that the molecular property of HLA-DQ measured by resistance to denaturation of the alphabeta dimer in SDS may play a role in IDDM protection.
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PMID:Exceptional stability of the HLA-DQA1*0102/DQB1*0602 alpha beta protein dimer, the class II MHC molecule associated with protection from insulin-dependent diabetes mellitus. 983 37

The NAPRTCS has enrolled 4,329 children who have received an index renal transplant since 1987. Seventy-three percent of the transplant recipients were children above 6 years of age. In the age group below 6 years rejection episodes are not more frequent, however the first acute rejection episode is frequently irreversible leading to graft failure. Many of the renal disorders that lead to ESRD and transplantation in adults, such as diabetes and hypertension, are less often observed in the pediatric population. Developmental disorders, such as renal dysplasia and obstructive uropathy, are frequent diagnostic entities, and the most common glomerular disorder leading to transplantation in children is focal segmental glomerulosclerosis. In an attempt to overcome dialysis-associated growth retardation many pediatric renal centers resort to preemptive transplantation, thus 24% of the children receiving a transplant have never undergone dialysis. Graft survival in these children is similar to that observed in children receiving maintenance dialysis, however accelerated growth is not noted. Catch-up growth, defined as gain of 1 SDS, is observed in 47% of children below the age of 6 years and in only 22% of children over the age of 6 years. Infants (below 2 years) have a higher mortality rate following transplantation compared to older children. Long-term (5-year) graft survival for children receiving a cadaver donor graft is 60%, and for living donor kidney recipients the graft survival is 76%. Due to changes in practice patterns, such as a judicious use of cadaver donors, increased use of prophylactic T-cell antibody, and better maintenance immunosuppression, cadaver donor graft survival has improved each year since 1987. The cohorts of children with a cadaver donor transplant in the years 1991 and 1992 have a 2-year graft survival which is 10% better than that observed in the earlier years.
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PMID:Pediatric renal transplantation--the NAPRTCS experience. 991 93

Vitamin B6 is essential for the metabolism of fat, carbohydrate and protein. In this study the effect of vitamin B6 on diabetes induced impairments in rat lenses was investigated. Although macroscopic examination revealed no opacification of rat lenses in any groups, uncontrolled induced diabetes caused significant decreases in lens glutathione and increases in lens protein nonenzymatic glycosylation and blood glucose. Administration of vitamin B6 did not inhibit these diabetes induced alterations significantly. SDS-polyacrylamide gel electrophoresis revealed some significant differences in some protein bands between groups.
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PMID:Effect of vitamin B6 on lenses of diabetic rats. 1009 11

Parsley (Petroselinum crispum) is one of the medicinal herbs used by diabetics in Turkey and it has been reported to reduce blood glucose. The purpose of this study therefore was to investigate the effect of feeding parsley on diabetes induced impairments in rat skins. Uncontrolled induced diabetes caused significant increases in nonenzymatic glycosylation of skin proteins, lipid peroxidation and blood glucose. Administration of parsley extract did not inhibit these effects except for the increase in blood glucose. SDS-polyacrylamide gel electrophoresis revealed no significant differences in any protein bands between any of the groups.
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PMID:Effect of parsley (Petroselinum crispum) on the skin of STZ induced diabetic rats. 1019 Jan 88

The authors have followed 18 prepubertal children (3-12 years of age) with Prader-Willi syndrome during 5 years of growth hormone (GH) treatment. Initially, all the children participated in a randomized, controlled GH trial, conducted to assess the effects of GH treatment on growth, body composition and behaviour. GH was administered to group A (n = 9) at a dose of 0.1 IU/kg/day (0.033 mg/kg/day) for 2 years. Group B (n = 9) was untreated for the first year, but the children were given GH at a dose of 0.2 IU/kg/day (0.066 mg/kg/day) during the second year. Thereafter, all children stopped GH treatment for 6 months and were then restarted with GH at a dose of 0.1 IU/kg/day (0.033 mg/kg/day). During the first year of GH treatment, there was a dramatic increase in height SDS in both groups. The attained height percentile was maintained during the continued GH treatment. Five years after the start of GH treatment, mean height SDS is still above average for age. Four children have reached final height, all within 2 SD of target height. During the first year of GH treatment, body mass index (BMI) SDS decreased significantly from 3.0 to 1.5 SDS in group A and from 2.8 to 1.2 SDS in group B, but it increased again during the 6-month period without treatment. Following the restart of GH treatment, BMI SDS has stabilized at 1.7 SDS for group A and 2.5 SDS for group B. In 16 of 18 patients, fasting insulin, glucose and the A1c fraction of glycosylated haemoglobin remained within normal ranges during 5 years of GH treatment. Following a period of rapid weight gain, two children have developed non-insulin-dependent diabetes mellitus. Glucose homeostasis returned to normal when GH treatment was withdrawn. In conclusion, GH treatment has a proven favourable effect on growth and body composition in patients with Prader-Willi syndrome. Treatment should be individualized, and close surveillance of glucose homeostasis is needed, especially if the patient is severely obese.
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PMID:Five years of growth hormone treatment in children with Prader-Willi syndrome. Swedish National Growth Hormone Advisory Group. 1062 58

In class II major histocompatibility complex (MHC) proteins, residue beta57 is usually aspartic acid. Alleles carrying serine, valine, or alanine at this position are strongly correlated with the development of insulin-dependent diabetes mellitus (IDDM). Asp(beta)57 participates in a conserved salt bridge that bridges the alpha and beta subunits in the peptide-binding site. It has been proposed that the correlation between IDDM and MHC alleles lacking Asp(beta)57 may be due to an instability of the protein caused by loss of this salt bridge. Using a pair of HLA-DQ proteins (alpha1*0201, beta1*0302) and (alpha1*0201, beta1*0303) differing only in having aspartic acid or alanine at position beta57, we show that the polymorphism does not have a significant effect on protein stability for either the empty or peptide-loaded forms. However, the circular dichroism spectra indicate that empty and peptide-loaded Alabeta57 proteins display slightly different secondary structures relative to their Aspbeta57 counterparts. A set of three peptides shows different binding affinities for DQ(alpha1*0201, beta1*0302) relative to DQ(alpha1*0201, beta1*0303). We propose that substitution of Asp(beta)57 residue causes a local rearrangement within the DQ peptide-binding site that alters the peptide-binding specificity. This rearrangement may help to explain the previously observed differences in SDS stability between Asp and non-Asp(beta)57 DQ proteins.
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PMID:Substitution of aspartic acid at beta57 with alanine alters MHC class II peptide binding activity but not protein stability: HLA-DQ (alpha1*0201, beta1*0302) and (alpha1*0201, beta1*0303). 1062 36

The accumulation of glucose exerts various cytotoxic effects on endothelial and other vascular cells, and thereby contributes to the development of microvascular complications in diabetes. Since tissues, in which vascular complications typically occur, do not take up glucose in an insulin regulated manner, it is an important question to know whether other mechanisms exist in these cells to restrict the uptake and the accumulation of glucose. To study this question, we used microvascular endothelial cells isolated from rat heart endothelial cells (RHEC). In RHEC, the non-insulin regulated glucose transporter (Glut-1) was detected as a broad protein band of 50-65 kD. In contrast, the Glut-1 from rat brain, which was taken as reference, had a molecular weight of 45 kD. After treatment with endoglycosidase F, both proteins formed a band of approximately 40 kD on SDS-PAGE, demonstrating a more extensive glycosylation of Glut-1 in RHEC as compared to brain. Incubation of the cells in high glucose (22 mM, up to 10 days) did not down-regulate either Glut-1 protein or mRNA. In contrast to high glucose, deprivation of the cells from glucose led to an increase in Glut-1 mRNA and protein which is partly non-glycosylated. In cells from hearts of streptozotocin-diabetic rats (DRHEC), Glut-1 protein, but not Glut-1 mRNA, was reduced by about 40%. Additionally, a significant amount of glycosyl residues was resistant to the enzymatic treatment with N-endoglycosidase F. Both changes in Glut-1 were also observed when the cells were cultivated in low glucose (5.5 mM) for several passages indicating a long lasting, hardly reversible modification of Glut-1 by diabetes. These data indicate that Glut-1 is not down-regulated in RHEC by high glucose, and that this important mechanism to protect the endothelium against an intracellular accumulation of glucose is missing in RHEC. As a consequence, increases in blood glucose may lead to a glucose overload with the described deleterious effects on the structure and function of endothelium.
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PMID:Diabetes mellitus induces long lasting changes in the glucose transporter of rat heart endothelial cells. 1066 16


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