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)

Mitochondrial DNA (mtDNA) mutation is associated with a subtype of non-insulin-dependent diabetes mellitus (NIDDM). We identified two homoplasmic mtDNA mutations at the positions of 3394 (T-C) and 3423 (G-T) in a NIDDM patient with clinical features of mitochondrial encephalopathy. The mtDNA 3394T-C mutation changed a conserved tyrosine to a histidine in NADH dehydrogenase subunit 1. The frequency of mtDNA 3994 T-C mutation was determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) in general NIDDM patients and nondiabetic control subjects. The mutation was seen in 4.9% of NIDDM patients and 1.3% of nondiabetic controls. It is indicated that the mtDNA 3394 T-C mutation is associated with NIDDM in Japan.
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PMID:Mitochondrial DNA 3394 mutation in the NADH dehydrogenase subunit 1 associated with non-insulin-dependent diabetes mellitus. 864 85

Studies suggest that thrombosis is important in the progression of atherosclerotic lesions. The biochemical markers prothrombin fragment 1-2 and fibrinopeptide A reflect in vivo thrombin generation and activity, respectively. As such, they are markers that might be associated with cardiovascular risk. From the Cardiovascular Health Study, a cohort study of 5201 persons over 65 years of age, 399 persons free of clinical cardiovascular disease (CVD) at the baseline examination were selected for study of specialized markers of hemostasis. We report the cross-sectional relationships of the thrombin markers to CVD risk factors and measures of subclinical CVD. The range of fragment 1-2 2 was 0.12 to 0.85 nmol/L. The range of fibrinopeptide A was 0.9 to 44.1 micrograms/L. High levels of fragment 1-2 and fibrinopeptide A were associated with age, with levels higher in women than men. Fragment 1-2 was associated with smoking; high levels of triglyceride, creatinine, and C-reactive protein; and low levels of glucose. Fibrinopeptide A was associated with high C-reactive protein and apolipoprotein(a) and lower ankle-brachial index. There were no significant associations of the thrombin markers with race, fibrinogen, alcohol consumption, diabetes, or most measures of subclinical CVD. Study findings support a hypothesis that there are physiological interrelationships between cardiac risk factors, hemostasis, inflammation, and progression of atherosclerosis.
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PMID:Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. 879 70

We have studied the genotypic, haplotypic, and allelic distribution of germline Restriction Fragment Length Polymorphism (RFLP) of T-cell receptor (Tcr) alpha, gamma, and delta loci in 75 insulin-dependent diabetes mellitus (IDDM) patients and 84 healthy blood donors as control population. The restriction endonuclease PvuII produces three allelic fragments of Tcr C gamma (TcrCG) gene segment of 16, 13, and 11.3 Kb respectively. Our observations revealed that PvuII/TcrCG RFLP allelic distributions were not significantly different in the IDDM and the control group. However, 85% of IDDM patients carried HLA DR3 and/or DR4 haplotypes, and when comparing these patients with a second group of HLA DR3+ and/or DR4+ healthy individuals, the 11.3 Kb/PvuII fragment of TcrCG gene was found to be associated with IDDM patients (chi 2 = 11.4, P = 0.003). 54.9% of IDDM patients carried at least one 11.3 Kb allele vs. 21% in controls (chi 2 = 10.77, P = 0.004). No significant association was found between RFLP in Tcr, C alpha, C delta, V gamma 9 loci and IDDM.
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PMID:T-cell receptor alpha, delta, and gamma chain genes in insulin-dependent diabetes mellitus. 909

ICA512/IA-2, a tyrosine phosphatase-like protein, is one of the major autoantigens in type 1 diabetes. Following phage display characterization of ICA512 autoantigenic epitopes, we developed fluid phase autoantibody radioimmunoassays for a series of ICA512 fragments (F1 [amino acids (aa): 761-964], F2A [aa 256-760], F2B [aa 761-928], and F2C [aa 929-979]). With the hypothesis that 'non-diabetes associated' ICA512 autoantibodies would differ from diabetes associated ICA512 autoantibodies in terms of epitopes recognized, we analyzed ten such serum samples (two from normal control individuals, one from a general population subject with transient ICA512 autoantibodies and seven from relatives of patients with type 1 diabetes who had single transient ICA512 positivity). All but one of the 'non-diabetes associated' ICA512 positive samples (9/10) did not react with Fragment 1 which contains the major antigenic epitopes of the molecule that were recognized by almost all (51/52) ICA512 positive new onset patient samples and pre-diabetic relatives (P< 10(-6)). The great majority of samples (44/52) from the new onset patients and pre-diabetic relatives reacted with at least two fragments and 60% (31/52) with three or more fragments. In contrast, only one sample of the ICA512 'non-diabetes associated' sera reacted with multiple fragments (P< 10(-4)). Our findings suggest that diabetes associated anti-ICA512 autoantibodies react with multiple ICA512 epitopes while non-diabetes associated ICA512 autoantibodies may usually represent reactivity of antibodies with determinants of ICA512 unrelated to type 1 diabetes. The ability to distinguish diabetes associated from non-diabetes associated anti-ICA512 autoantibodies should provide prognostic information and more importantly suggests that even with highly specific radioassays positivity may occur unrelated to type 1 diabetes.
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PMID:ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies. 1190 51

Lower extremity ischemia is one aspect of atherosclerosis, a disease associated with both inflammation and hypercoagulability. Many recent studies have focused on a diversity of mechanisms by which inflammation can promote blood clotting. However, it has not been proven that inflammation can actually trigger clinically relevant thrombus formation in vivo. The purpose of the study was to determine the plasma levels of markers of inflammation and their possible association with markers for coagulability with special emphasis on the difference between patients with and without diabetes. Forty-six patients, 20 diabetics and 26 without diabetes scheduled for lower extremity revascularisation were examined by preoperative blood sampling. A strong positive correlation between C-reactive protein (CRP) and fibrinogen was found, particularly in diabetics. A high fibrinogen level was not associated with other markers of hypercoagulability, Thrombin-Antithrombin (TAT), Prothrombin Fragment 1+2 (F 1+2) and D-dimer although the latter three correlated with each other. There was also a correlation between von Willebrand antigen (vWF) and CRP, also in this case the relationship was dependent on the findings in patients with diabetes. It is concluded that there is a difference between diabetic and nondiabetic patients with lower limb ischemia with the former showing stronger signs of inflammation.
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PMID:Markers of inflammation and hypercoagulability in diabetic and nondiabetic patients with lower extremity ischemia. 1206 38

Apoptosis of pancreatic beta cells is implicated in the onset of type 1 and type 2 diabetes. Consequently, strategies aimed at increasing the resistance of beta cells toward apoptosis could be beneficial in the treatment of diabetes. RasGAP, a regulator of Ras and Rho GTPases, is an atypical caspase substrate, since it inhibits, rather than favors, apoptosis when it is partially cleaved by caspase-3 at position 455. The antiapoptotic signal generated by the partial processing of RasGAP is mediated by the N-terminal fragment (fragment N) in a Ras-phosphatidylinositol 3-kinase-Akt-dependent, but NF-kappaB-independent, manner. Further cleavage of fragment N at position 157 abrogates its antiapoptotic properties. Here we demonstrate that an uncleavable form of fragment N activates Akt, represses NF-kappaB activity, and protects the conditionally immortalized pancreatic insulinoma betaTC-tet cell line against various insults, including exposure to genotoxins, trophic support withdrawal, and incubation with inflammatory cytokines. Fragment N also induced Akt activity and protection against cytokine-induced apoptosis in primary pancreatic islet cells. Fragment N did not alter insulin cell content and insulin secretion in response to glucose. These data indicate that fragment N protects beta cells without affecting their function. The pathways regulated by fragment N are therefore promising targets for antidiabetogenic therapy.
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PMID:Expression of an uncleavable N-terminal RasGAP fragment in insulin-secreting cells increases their resistance toward apoptotic stimuli without affecting their glucose-induced insulin secretion. 1604 10

Aberrant activation of the phosphoinositide 3-kinase pathway because of genetic mutations of essential signalling proteins has been associated with human diseases including cancer and diabetes. The pivotal role of 3-phosphoinositide-dependent kinase-1 in the PI3K signalling cascade has made it an attractive target for therapeutic intervention. The N-terminal lobe of the 3-phosphoinositide-dependent kinase-1 catalytic domain contains a docking site which recognizes the non-catalytic C-terminal hydrophobic motifs of certain substrate kinases. The binding of substrate in this so-called PDK1 Interacting Fragment pocket allows interaction with 3-phosphoinositide-dependent kinase-1 and enhanced phosphorylation of downstream kinases. NMR spectroscopy was used to a screen 3-phosphoinositide-dependent kinase-1 domain construct against a library of chemically diverse fragments in order to identify small, ligand-efficient fragments that might interact at either the ATP site or the allosteric PDK1 Interacting Fragment pocket. While majority of the fragment hits were determined to be ATP-site binders, several fragments appeared to interact with the PDK1 Interacting Fragment pocket. Ligand-induced changes in 1H-15N TROSY spectra acquired using uniformly 15N-enriched PDK1 provided evidence to distinguish ATP-site from PDK1 Interacting Fragment-site binding. Caliper assay data and 19F NMR assay data on the PDK1 Interacting Fragment pocket fragments and structurally related compounds identified them as potential allosteric activators of PDK1 function.
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PMID:Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments. 1920 20

The caspase-3-generated RasGAP N-terminal fragment (fragment N) inhibits apoptosis in a Ras-PI3K-Akt-dependent manner. Fragment N protects various cell types, including insulin-secreting cells, against different types of stresses. Whether fragment N exerts a protective role during the development of type 1 diabetes is however not known. Non-obese diabetic (NOD) mice represent a well-known model for spontaneous development of type 1 diabetes that shares similarities with the diseases encountered in humans. To assess the role of fragment N in type 1 diabetes development, a transgene encoding fragment N under the control of the rat insulin promoter (RIP) was back-crossed into the NOD background creating the NOD-RIPN strain. Despite a mosaic expression of fragment N in the beta cell population of NOD-RIPN mice, islets isolated from these mice were more resistant to apoptosis than control NOD islets. Islet lymphocytic infiltration and occurrence of a mild increase in glycemia developed with the same kinetics in both strains. However, the period of time separating the mild increase in glycemia and overt diabetes was significantly longer in NOD-RIPN mice compared to the control NOD mice. There was also a significant decrease in the number of apoptotic beta cells in situ at 16 weeks of age in the NOD-RIPN mice. Fragment N exerts therefore a protective effect on beta cells within the pro-diabetogenic NOD background and this prevents a fast progression from mild to overt diabetes.
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PMID:RasGAP-derived fragment N increases the resistance of beta cells towards apoptosis in NOD mice and delays the progression from mild to overt diabetes. 2179 17

There is growing evidence the microbiota of the large bowel may influence the risk of developing colorectal cancer as well as other diseases including type-1 diabetes, inflammatory bowel diseases and irritable bowel syndrome. Current sampling methods to obtain microbial specimens, such as feces and mucosal biopsies, are inconvenient and unappealing to patients. Obtaining samples through rectal swabs could prove to be a quicker and relatively easier method, but it is unclear if swabs are an adequate substitute. We compared bacterial diversity and composition from rectal swabs and rectal mucosal biopsies in order to examine the viability of rectal swabs as an alternative to biopsies. Paired rectal swabs and mucosal biopsy samples were collected in un-prepped participants (n = 11) and microbial diversity was characterized by Terminal Restriction Fragment Length polymorphism (T-RFLP) analysis and quantitative polymerase chain reaction (qPCR) of the 16S rRNA gene. Microbial community composition from swab samples was different from rectal mucosal biopsies (p = 0.001). Overall the bacterial diversity was higher in swab samples than in biopsies as assessed by diversity indexes such as: richness (p = 0.01), evenness (p = 0.06) and Shannon's diversity (p = 0.04). Analysis of specific bacterial groups by qPCR showed higher copy number of Lactobacillus (p < 0.0001) and Eubacteria (p = 0.0003) in swab samples compared with biopsies. Our findings suggest that rectal swabs and rectal mucosal samples provide different views of the microbiota in the large intestine.
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PMID:Differences in microbial signatures between rectal mucosal biopsies and rectal swabs. 2306 16

Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P=0.042), the 'G' allele association being highly significant (P=0.022). Further analysis showed that individuals with 'GG' haplotype were at increased risk of T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population.
Diabetes Metab Syndr
PMID:Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with type 2 diabetes in North Indians. 2315 72


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