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)

A 6-week-old child presented with hypotonia, myopathy, and a rapidly worsening dilated cardiomyopathy with severe atrial and ventricular arrhythmias and pulmonary hypertension, which proved fatal at age 3 months. Biochemical analysis showed a combined deficiency of the enzymatic activities of complexes I and IV and molecular studies identified a T14709C mutation in the mitochondrial tRNA glutamic acid gene. A review of symptomatology in patients with this mutation shows that it mainly presents in childhood or young adults with mild myopathy and diabetes mellitus. Infants with a high, nearly homoplasmic mutant load can present with more severe symptoms including cardiomyopathy. Families with this mitochondrial DNA mutation should be aware that increased mutant load in a subsequent generation may result in severe and often fatal cardiac symptoms.
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PMID:Infantile cardiomyopathy caused by the T14709C mutation in the mitochondrial tRNA glutamic acid gene. 1789 17

Transplantation of pancreatic islet cells is the only known potential cure for diabetes mellitus. However, the difficulty in obtaining sufficient numbers of purified islets for transplantation severely limits its use. A renewable and clinically accessible source of stem cells capable of differentiating into insulin-secreting beta-cells might circumvent this limitation. Here, we report that human fetal bone marrow (BM)-derived mesodermal progenitor cells (MPCs) possess the potential to generate insulinsecreting islet-like clusters (ISILCs) when injected into human fetal pancreatic tissues implanted in severe combined immunodeficiency (SCID) mice. Seven essential genes involved in pancreatic endocrine development, including insulin, glucagon, somatostatin, pdx-1, glut-2, nkx 2.2, and nkx 6.1, are expressed in these BM-MPC-derived ISILCs, suggesting that ISILCs are generated through neogenesis of BM-MPCs. Our data further suggest that differentiation of BM-MPCs into ISILCs is not mediated by cell fusion. Insulin secretion from these ISILCs is regulated by glucose concentration in vitro, and transplantation of purified ISILCs normalizes hyperglycemia in streptozocin (STZ)- induced nonobese diabetic (NOD)/SCID mice.
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PMID:Human marrow-derived mesodermal progenitor cells generate insulin-secreting islet-like clusters in vivo. 1799 97

An alpha-amylase inhibitor (alpha-AI) was isolated from white kidney beans (Phaseolus vulgaris L) by ethanol fractional precipitation, ion exchange chromatography and gel filtration column chromatography. It was a homogeneity glycoprotein demonstrated by SDS-PAGE and gel filtration on CL-6B. The glycoprotein contained 88.2% protein and was rich in aspartic acid, glutamic acid, leucine, threonine and serine. The carbohydrate moiety was consisted of Man, Glc, Gal and Xyl in a mole ratio of 2.42: 1.50: 1.52: 1.00. The glycan and the core protein backbone was connected by O-linkage as determined by beta-elimination reaction. The continuous oral administration of the alpha-AI (150 mg x kg(-1) x d(-1)) for 7 days can lower fasting blood glucose and 300 mg x kg(-1) x d(-1) alpha-AI for 7 days can improve the sugar tolerance on alloxan-dependent diabetic model rats. The result showed the alpha-AI obtained from white kidney beans had good hypoglycemic effect on alloxan induced diabetic rats and may have high potential pharmaceutical value as a regulative digestive-starch degradation in patients suffering from diabetes.
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PMID:Isolation and activity of an alpha-amylase inhibitor from white kidney beans. 1833 41

Two biallelic polymorphisms, previously described in the human intercellular adhesion molecule (ICAM)-1 gene at codon 241 (glycine [G] to arginine [R] substitution) and codon 469 (glutamic acid [E] to lysine [K] substitution) have been associated with a number of diseases including myocardial infarction, transplant rejection, and diabetes. However, the functional significance of these polymorphisms has not been determined. ICAM-1 cell surface expression and ICAM-1-mediated leukocyte adhesion were investigated using Cos7 transfected with ICAM-1 polymorphic variants or human umbilical vein endothelial cells (HUVEC) of different ICAM-1 genotypes. There was significantly higher expression of surface ICAM-1 on Cos7 transfected with a plasmid encoding the GE (G241/E469) ICAM-1 variant or untreated HUVEC of GEGE (G241/E469 homozygous genotype). ICAM-1-mediated adhesion of peripheral blood mononuclear cells (PBMC) to GE-Cos7 cells or TNF-treated GEGE HUVEC was significantly increased. However, there was no significant difference in adhesion of PBMC to recombinant ICAM-1 of each polymorphic variant plated onto plastic wells. We conclude that the GE genotype of ICAM-1 is associated with greater cell surface expression of ICAM-1, which in turn leads to greater adhesion of leukocytes. This may explain the previously described associations of ICAM-1 polymorphisms with chronic inflammatory disease.
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PMID:Expression of endothelial intercellular adhesion molecule-1 is determined by genotype: effects on efficiency of leukocyte adhesion to human endothelial cells. 1836 30

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.
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PMID:Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. 1907 94

In our preliminary screening study on the anti-inflammatory activity, eight triterpenes, one sterol, and one chalcone were isolated from the CH(2)Cl(2)-soluble extract of the stems and leaves of Rhus sylvestris Siebold and Zucc (Anacardiaceae). On the basis of their spectroscopic data, these compounds were identified as 10alpha-cucurbitadienol (1), glut-5-en-3-ol (2), beta-amyrin acetate (3), beta-amyrin (4) and lupeol (5), cycloart-24-en-3-one (6), cycloart-25-en-3,24-dione (7), 24-hydroxycycloart-25-en-3-one (8), beta-sitosterol (9), and 2'-hydroxy-4,4'-dimethoxychalcone (10). All of them were isolated from this plant for the first. Furthermore, the compounds in non-cytotoxic concentrations (0-1.0microM) were tested for their ability to block inflammatory cytokine secretion in the presence of LPS in the murine RAW264.7 macrophage cell line. Among the compounds that were tested, compounds 8 and 9 reduced the LPS-induced secretion of IL-6, as well as TNF-alpha, in a mouse RAW264.7 macrophage cell line. Moreover, compounds 2, 3, 7, and 10 specifically diminished only the secretion of TNF-alpha even in 0.01microM concentrations. It is thus suggested that they are potential therapeutics of TNF-alpha-related diseases and conditions, such as transplant rejection, type II diabetes, and atherosclerosis.
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PMID:The regulation of inflammatory cytokine secretion in macrophage cell line by the chemical constituents of Rhus sylvestris. 1944 18

In this study, we compared the rate of insulin requirement among adults with type 1 diabetes (T1D) in 24 Ukrainian regions. The glutamic acid decaroxylase 65 antibody (GADA), insulin antibody (IA), and plasma c-peptide levels were investigated. The data included the prevalent cases of T1D in Ukraine at the end of 2006. Only persons aged over 14 years at the time of inclusion into the Ukrainian register and diagnosed with diabetes before 30 years of age were included in this study (n=26796). A total of 86 T1D patients (42 males; 44 females) with a mean age of 27.5 years (0.86) and a mean diabetes duration of 10.3 (0.72) years (SE), were randomly selected from four regional diabetes registers. The GADA, IA, and the plasma c-peptide levels were also determined. The logistic regression model was used, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Furthermore, the differences in the T1D prevalence among the 24 Ukrainian regions were obtained (p<0.001). In the "minimal" regional cluster (MIC), the prevalence rate was 6 (5-6), and in the "maximal" (MAC) regional cluster, it was -9 (8-9) per 10000 adults. For patients with a disease duration (DD) of up to 15 years (n=13677), the daily insulin dose (DID) was observed to increase linearly with DD (R=0.899, p<0.001). The median insulin doses were standardized according to DD, and the values were lowest in the MIC and highest in the MAC populations: 45.89 (45.28-47.19) and 56.59 (53.33-57.88) U/24 h, respectively (p<0.01). Furthermore, the level of HbA1c in the MAC of T1D patients was observed to be higher than that in the MIC (9.52+/-2.24%, n=240, and 8.57+/-3.29%, n=111, respectively; p<0.01). In addition, the GADA levels and persistence in the MAC patients (n=38) were higher than that in the MIC patients (n=48): 14.1+/-4.6 and 3.2+/-1.2 U/ml, respectively, mean+/-SE; p=0.028; OR=9.66 (3.31-28.17), p<0.001. Adjusting for age, gender, and duration of diabetes affected the results only slightly. Furthermore, the IA and c-peptide levels and their persistence were not observed to be associated with TD1 prevalence.
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PMID:Correlation between the prevalence of type 1 diabetes with the daily insulin dose and the autoimmune process against glutamic acid decarboxylase in adults. 1978 23

Numerous reports have demonstrated an active role for proinsulin C-peptide in ameliorating chronic complications associated with diabetes mellitus. It has been recently reported that some of these activities are dependent upon activation of C-peptide with certain metal ions, such as Fe(II), Cr(III) or Zn(II). In an effort to gain a greater understanding of the structure/function dependence of the peptide-metal interactions responsible for this activity, a series of experiments involving the use of electrospray ionization (ESI), matrix assisted laser desorption/ionization (MALDI) and collision-induced dissociation-tandem mass spectrometry (CID-MS/MS) of C-peptide in the presence or absence of Zn(II) have been carried out. Additionally, various C-peptide mutants with alanine substitution at individual aspartic acid or glutamic acid residues throughout the C-peptide sequence were analyzed. CID-MS/MS of wild type C-peptide in the presence of Zn(II) indicated multiple sites for metal binding, localized at acidic residues within the peptide sequence. Mutations of individual acidic residues did not significantly affect this fragmentation behavior, suggesting that no single acidic residue is critical for binding. However, ESI-MS analysis revealed an approximately 50% decrease in relative Zn(II) binding for each of the mutants compared to the wild type sequence. Furthermore, a significant decrease in activity was observed for each of the Zn(II)-activated mutant peptides compared to the wild type C-peptide, indicated by measurement of ATP released from erythrocytes, with a 75% decrease observed for the Glu27 mutant. Additional studies on the C-terminal pentapeptide of C-peptide EGSLQ, as well as a mutant C-terminal pentapeptide sequence AGSLQ, revealed that substitution of the glutamic acid residue resulted in a complete loss of activity, implicating a central role for Glu27 in Zn(II)-mediated C-peptide activity.
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PMID:Mass spectrometric characterization and activity of zinc-activated proinsulin C-peptide and C-peptide mutants. 2009 59

Poly-gamma-glutamic acid (gamma-PGA) prepared by fermentation of microbe was used as drug carrier for vanadium sulfate to obtain vanadyl-poly-gamma-glutamic acid (VO-gamma-PGA) complex. The FI-IR spectrum of the complex demonstrated that the expected VO-gamma-PGA complex is formed by the coordination of VO(2+) through the side chain carboxylic groups of the gamma-PGA. Studies of the complex in treating type I diabetes were carried out on alloxan induced diabetes rats. The results of treating the rats in 2 weeks and then stopping administration for 10 days showed that VO-gamma-PGA can effectively lower blood glucose levels of diabetic rats during administration. But after ceasing treatment there were no differences between groups in blood glucose level and water intake. The results of oral glucose tolerance and some serum parameters also demonstrated that VO-gamma-PGA was more effective than vanadium sulfate in treating diabetic rats.
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PMID:Effects of insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex on diabetic rat model. 2012 19

Immunomodulatory strategies in the management of type 1 diabetes mellitus (T1DM) have as their primary target the prevention of initiating islet autoimmunity (primary-), the secondary one is the progression to diabetes (secondary-) in non-diabetic persons at risk, and the decline of beta-cell function in new-onset patients (tertiary-prevention). This article reviews four recent immunointervention trials in patients with T1DM. (1) The Pre-POINT study is a primary prevention trial that will test whether vaccination with oral or nasal insulin can prevent the progression of islet autoimmunity and of T1DM in autoantibody-negative children who are genetically at high diabetes risk. (2) The Cord Blood study is a tertiary immunointervention trial that will test whether administration of autologous umbilical cord blood to children with T1DM can lead to regeneration of pancreatic islet insulin-producing beta-cells and improved blood glucose control. (3) The GAD Vaccination study will test whether vaccination with alum-formulated rhGAD65 (recombinant human glutamic acid decarboxylate) can preserve beta-cell function in 320 children with newly diagnosed T1DM, as has been suggested in a recent phase II study. (4) The AIDA study will test the beta-cell protective effect of interleukin-1-receptor antagonist Anakinra in 80 patients with T1DM, which has recently been shown to improve beta-cell function in patients with type 2 diabetes.
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PMID:[Survey of recent clinical trials of the prevention and immunointervention of type 1 diabetes mellitus]. 2016


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